Asper Biogene – genetic testing company

List of diseases covered by Palmoplantar Keratoderma NGS panel

Palmoplantar Keratoderma NGS panel

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Differential diagnosis of palmoplantar keratoderma types/subtypes and other genetically/phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling

Palmoplantar keratoderma (PPK) is a group of skin conditions characterized by hyperkeratosis on the surface of the palms of the hands and soles of the feet. Various clinically, histopathologically and genetically distinct phenotypes can be diagnosed. PPK can also be a feature of various underlying syndromes. PPK can be either acquired during the lifetime (more commonly) or inherited. Early onset and positive family history suggest a genetic cause. Inherited PPKs are classified on the basis of the clinical and histological descriptions of the lesions (epidermolytic or nonepidermolytic hyperkeratosis), the mode of inheritance (e.g. autosomal dominant or recessive), the age of onset, the presence of other skin lesions, the association with systemic anomalies, the biochemical defect, and/or the genetic mutation.

The test covers known genetic causes of PPK types/ subtypes and a range of other genetically/ phenotypically related disorders.

Depending on the gene involved, it could be inherited in an autosomal dominant or autosomal recessive pattern.

The incidence and prevalence of hereditary PPK are not available. The most types of hereditary PPK are rare, but the actual number of affected individuals may be underestimated because of mild symptoms, leading to fewer laboratory‐confirmed cases.

References:
Bodemer C, Steijlen P, Mazereeuw-Hautier J, O’Toole EA. Treatment of hereditary palmoplantar keratoderma: a review by analysis of the literature [published online ahead of print, 2020 Apr 20]. Br J Dermatol. 2020;10.1111/bjd.19144. doi:10.1111/bjd.19144. PMID: 32307694
Has C, Technau-Hafsi K. Palmoplantar keratodermas: clinical and genetic aspects. J Dtsch Dermatol Ges. 2016;14(2):123-140. doi:10.1111/ddg.12930. PMID: 26819106
Hennies HC, Küster W, Mischke D, Reis A. Localization of a locus for the striated form of palmoplantar keratoderma to chromosome 18q near the desmosomal cadherin gene cluster. Hum Mol Genet. 1995;4(6):1015-1020. doi:10.1093/hmg/4.6.1015. PMID: 7544663

List of diseases covered by
Oculocutaneous Albinism, Ocular Albinism, Hermansky-Pudlak Syndrome, Chediak-Higashi Syndrome
NGS panel

Oculocutaneous Albinism, Ocular Albinism, Hermansky-Pudlak Syndrome, Chediak-Higashi Syndrome
NGS panel

Deletion/duplication analysis

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of different forms/subtypes of Oculocutaneous albinism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome and other genetically/phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling

Oculocutaneous albinism (OCA) is a group of rare inherited disorders characterized by a reduction or complete lack of melanin pigment in the skin, hair and eyes. These conditions are caused by mutations in specific genes that are relevant to the production of melanin pigment in melanocytes. Patients usually have vision problems such as reduced sharpness, nystagmus and photophobia. There are seven types of OCA (OCA1-7) caused by mutations in seven different genes.

Ocular albinism (OA) primarily affects the eyes, and does not significantly affect the color of the skin and hair. The most common form of OA is type 1 (OA1), also named X-linked ocular albinism. OA1 is characterized by vision abnormalities in affected males. Vision deficits are present at birth and do not become more severe over time. Other forms of OA are much rarer and may be associated with additional signs and symptoms such as hearing loss.

Hermansky-Pudlak syndrome (HPS) is a multisystem, hereditary disorder characterized mainly by albinism with visual impairment and blood platelet dysfunction with prolonged bleeding. The symptoms of HPS are present at birth. It is the third most prevalent form of albinism. There are 11 types of HPS (1-11), which can be distinguished by their signs and symptoms and underlying genetic cause.

Chediak-Higashi syndrome (CHS) is an inherited, complex, immune disorder that usually occurs in childhood (at birth or shortly thereafter) characterized by oculocutaneous albinism, nervous system abnormalities, immune deficiency with an increased susceptibility to infections, and a tendency to easy bruising and abnormal bleeding.

The test covers known genetic causes of all aforementioned syndromes.

Oculocutaneous albinism, Hermansky-Pudlak syndrome, and Chediak-Higashi syndrome are inherited in an autosomal recessive inheritance pattern. Ocular albinism type 1 is inherited in an X-linked pattern.

Oculocutaneous albinism occurring in all populations, with an estimate prevalence of 1:20 000 people worldwide. Ocular albinism type 1 affects at least 1: 60 000 males. Hermansky-Pudlak syndrome is estimated to affect 1:500 000 to 1 000 000 individuals worldwide. Type 1 is more common in the northwestern part of Puerto Rico where about 1: 1800 people are affected. Type 3 is common in people from central Puerto Rico. Chediak-Higashi syndrome is a very rare disorder. About 200 cases of the condition have been reported worldwide. 85% of affected individuals progress the accelerated phase.

References:
Hayashi M, Suzuki T. Oculocutaneous Albinism Type 4. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; November 17, 2005. PMID:20301683
Huizing M, Malicdan MCV, Gochuico BR, et al. Hermansky-Pudlak Syndrome. 2000 Jul 24 [Updated 2017 Oct 26]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. PMID: 20301464
Huizing M, Malicdan MCV, Wang JA, et al. Hermansky-Pudlak syndrome: Mutation update. Hum Mutat. 2020;41(3):543-580. doi:10.1002/humu.23968. PMID:31898847
Lewis RA. Oculocutaneous Albinism Type 1. 2000 Jan 19 [Updated 2013 May 16]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. PMID:20301345
Lewis RA. Oculocutaneous Albinism Type 2. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; July 17, 2003. PMID: 20301410
Lewis RA. Ocular Albinism, X-Linked. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; March 12, 2004. PMID:20301517
Merideth MA, Introne WJ, Wang JA, O’Brien KJ, Huizing M, Gochuico BR. Genetic variants associated with Hermansky-Pudlak syndrome. Platelets. 2020;31(4):544-547. doi:10.1080/09537104.2019.1663810. PMID:32436471
Pennamen P, Le L, Tingaud-Sequeira A, et al. BLOC1S5 pathogenic variants cause a new type of Hermansky-Pudlak syndrome [published online ahead of print, 2020 Jun 22]. Genet Med. 2020;10.1038/s41436-020-0867-5. doi:10.1038/s41436-020-0867-5. PMID:32565547
Toro C, Nicoli ER, Malicdan MC, Adams DR, Introne WJ. Chediak-Higashi Syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; March 3, 2009. PMID:20301751

Neurofibromatosis NGS panel

Indications for genetic testing: 
1. Confirmation of clinical diagnosis
2. Differential diagnosis of neurofibromatosis types and other genetically/phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling

Neurofibromatosis (NF) is a group of neurocutaneous syndromes characterized by generally non-cancerous tumors in the nervous system and skin. The tumors involve the supporting cells of the nervous system rather than the neurons. There are three types of NF:
1) NF1 is characterized by skin changes (cafe-au-lait spots, freckling in armpit and groin area), bone abnormalities, optic gliomas, and tumors on the nerve tissue or under the skin. Signs and symptoms are usually present at birth.
2) NF2 is characterized by acoustic neuromas, hearing loss, tinnitus, loss of balance, brain and/or spinal tumors, cataracts at a young age, secondary to bilateral vestibular schwannomas, and may have café-au-lait macules. NF2 often starts in the teen years.
3) Schwannomatosis (SWN) is characterized by multiple schwannomas (benign tumors of the nervous system) and, less frequently, meningiomas. Signs and symptoms of the condition vary based on the size, location and number of schwannomas but may include chronic pain, numbness, tingling, and/or weakness in the fingers and toes. SWN often develops during adulthood between ages 25 and 30.

The diagnosis of NF types is typically based on symptoms, examination, medical imaging, and biopsy.

The test covers known genetic causes of inherited forms of NF and a range of disorders with NF symptoms. Currently, many of the causative genes have not been identified yet.

All three types of NF are inherited in an autosomal dominant pattern. About 50% of NF1 and NF2 patients have a de novo mutation, and the other half have an inherited mutation. NF1 and NF2 have a nearly 100% penetrance with variable expressivity. Unlike most other autosomal dominant conditions, two copies of the NF1 and NF2 gene must be altered to trigger tumor formation in NF1 and NF2, respectively. A somatic mutation in the second copy of the NF1 gene or the NF2 gene occurs during a person’s lifetime in cells of the nervous system.

Inherited forms of the SWN account for 15% of all cases with highly variable expressivity and reduced penetrance (50%).

NF1 consisting of about 96% of all NF cases with a worldwide prevalence of 1:3000. NF2 consisting of about 3% of all NF with a worldwide prevalence between 1:25000 and 1:40000. SWN is the rarest type out of these three conditions with a worldwide prevalence 1:69000.

References:

Asthagiri AR, Parry DM, Butman JA, et al. Neurofibromatosis type 2. Lancet. 2009;373(9679):1974-1986. doi:10.1016/S0140-6736(09)60259-2. PMID:19476995
Cervi F, Saletti V, Turner K, et al. The TAND checklist: a useful screening tool in children with tuberous sclerosis and neurofibromatosis type 1. Orphanet J Rare Dis. 2020;15(1):237. Published 2020 Sep 7. doi:10.1186/s13023-020-01488-4. PMID:32894194
Farschtschi S, Mautner VF, McLean ACL, Schulz A, Friedrich RE, Rosahl SK. The Neurofibromatoses. Dtsch Arztebl Int. 2020;117(20):354-360. doi:10.3238/arztebl.2020.0354. PMID:32657748
Le C, Bedocs PM. Neurofibromatosis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 10, 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459329/.  PMID:29083784
Tiwari R, Singh AK. Neurofibromatosis Type 2. [Updated 2020 Aug 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470350/. PMID:29261934
Troullioud Lucas AG, Mendez MD. Neurocutaneous Syndromes. [Updated 2020 Aug 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537001/. PMID:30725686
Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B, Maria BL. Neurofibromatosis type 1 revisited. Pediatrics. 2009;123(1):124-133. doi:10.1542/peds.2007-3204. PMID:19117870

Melanoma
NGS panel

Del/dup analysis

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Testing of individuals with family history of cutaneous malignant melanoma
3. Testing of at-risk family members for known mutations
4. Genetic counseling

Cutaneous malignant melanoma (CMM) is the third most common type of skin cancer and most common melanoma subtype accounting for more than 90% of cases worldwide. Malignant melanoma is a neoplasm of pigment-producing cells called melanocytes that occurs mostly in skin but may also occur in noncutaneous sites such as eye, ear, urinary and gastrointestinal tract, leptomeninges, and oral and genital mucous membrane.

A significant risk factor for CMM is ultraviolet (UV) radiation. Thus, CMM is potentially preventable by diminishing exposure to UV radiation. However, other risk factors including numbers of naevi, eye and hair colour, freckles, familial history and genetic predisposition also play an important role in the risk of developing melanoma.

The most commonly applied clinical prediction rule is the ABCDE rule: Asymmetry, irregular Borders, more than one or uneven distribution of Colour, Diameter greater than 6 mm, and Evolution of moles. One third of CMMs appear from preexisting naevi (including both acquired and congenital types), whereas the rest appear to arise de novo. The presence of numerous melanocytic naevi (normal or atypical) confers the risk of CMM development.

Up to date, there are four major types of CMM: 1) the superficial spreading melanoma – 70% of CMMs; 2) the nodular melanoma – 15% to 30% of CMMs; 3) the lentigo maligna melanoma (or melanoma in situ) – less than 5% of CMMs; 4) the acral lentiginous variety – less than 5% of all CMMs, but accounts for 35% to 65% of CMMs diagnosed in dark-skinned individuals (African Americans, Asians, and Hispanics).

Light-skinned people have a 20 times greater risk of developing melanoma than dark-skinned people. The incidence of CMM in most developed countries has been steadily rising at least 4–6% per annum in recent decades. CMM accounting for 3% of all skin cancers, it results in 65% of all skin cancer deaths.

The test covers the most known genetic causes of CMM types.

The most cases of CMM are sporadic. A family history of CMM can be documented in 6% to 12% of new cases. Members of affected families share 50% cumulative lifetime risk of developing CMM. The familial CMM is inherited in an autosomal dominant pattern.

Incidence rate of CMM is 2.8–3.1 per 100,000 worldwide. There is a significant variation between countries, with the highest rate reported in Australia (37 per 100,000) and the lowest in South-Central Asia (0.2 per 100,000). In the United States, melanoma is the fifth most common cancer in men, affecting 30 in 100,000 men per year, and the sixth most common cancer in women, affecting 18 in 100,000 women per year. In Europe the incidence rate of CMM is lower compared with Australia and the United States, but within Europe incidence rates vary widely: Switzerland has the highest rates (19.2 per 100,000) and Greece the lowest rates (2.2 per 100,000).

References:
Ali Z, Yousaf N, Larkin J. Melanoma epidemiology, biology and prognosis. EJC Suppl. 2013;11(2):81-91. doi:10.1016/j.ejcsup.2013.07.012. PMID: 26217116
Badenas C, Aguilera P, Puig-Butillé JA, Carrera C, Malvehy J, Puig S. Genetic counseling in melanoma. Dermatol Ther. 2012;25(5):397-402. doi:10.1111/j.1529-8019.2012.01499.x. PMID: 23046018
Bashford MT, Kohlman W, Everett J, Parrott A, Pollin TI; Practice Guidelines Committee of the National Society of Genetic Counselors and the Professional Practice and Guidelines Committee of the American College of Medical Genetics and Genomics. Addendum: A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2019;21(12):2844. doi:10.1038/s41436-019-0586-y. PMID: 31332281
Cummins DL, Cummins JM, Pantle H, Silverman MA, Leonard AL, Chanmugam A. Cutaneous malignant melanoma. Mayo Clin Proc. 2006;81(4):500-507. doi:10.4065/81.4.500. PMID: 16610570
Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL; Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med. 2015;17(1):70-87. doi:10.1038/gim.2014.147. PMID: 25394175
Harrington E, Clyne B, Wesseling N, et al. Diagnosing malignant melanoma in ambulatory care: a systematic review of clinical prediction rules. BMJ Open. 2017;7(3):e014096. Published 2017 Mar 6. doi:10.1136/bmjopen-2016-014096. PMID: 28264830
Rigel DS, Friedman RJ, Kopf AW, Polsky D. ABCDE- an evolving concept in the early detection of melanoma. Arch Dermatol. 2005;141(8):1032-1034. doi:10.1001/archderm.141.8.1032. PMID: 16103334
Soura E, Eliades PJ, Shannon K, Stratigos AJ, Tsao H. Hereditary melanoma: Update on syndromes and management: Emerging melanoma cancer complexes and genetic counseling. J Am Acad Dermatol. 2016;74(3):411-422. doi:10.1016/j.jaad.2015.08.037. PMID: 26892651

Ichthyosis NGS panel

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of nonsyndromic ichthyoses forms/subtypes and other
genetically/phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling

Inherited ichthyoses are a group of rare genetic skin diseases characterized by hyperkeratosis and/or scaling skin. These manifestations are due to mutations in genes mostly involved in skin barrier formation. Inherited ichthyoses are divided into two major subdivisions: nonsyndromic ichthyoses and syndromic forms. The various forms of ichthyosis are distinguished from one another by: 1) the extent of scaling over the body; 2) the presence or absence and intensity of erythroderma; 3) the mode of inheritance; 4) the character of associated abnormalities. The specific symptoms and severity can vary among individuals with the same form. The most common ichthyoses as ichthyosis vulgaris and recessive X-linked ichthyosis often have a delayed onset compared with the other nonsyndromic ichthyoses.

The test covers known genetic causes of inherited forms of nonsyndromic ichthyoses and a range of disorders with ichthyosis symptoms. Currently, many of the causative genes have not been identified yet.

Nonsyndromic ichthyoses can be inherited in an autosomal dominant, autosomal recessive, or X-linked recessive inheritance pattern.

The ichthyoses are rare disorders occurring in all populations. Incidences vary according to disease type. The most common is ichthyosis vulgaris, with an estimate incidence of 1:250 to 1:1000. The recessive X-linked ichthyosis is the second most common ichthyosis, with a prevalence of 1:2000 to 1:6000.

References:
Oji V et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Sorèze 2009. J Am Acad Dermatol. 2010;63(4):607-641. doi:10.1016/j.jaad.2009.11.020. PMID: 20643494
Richard G. Autosomal Recessive Congenital Ichthyosis. 2001 Jan 10 [Updated 2017 May 18]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1420/
Takeichi T, Akiyama M. Inherited ichthyosis: Non-syndromic forms. J Dermatol. 2016;43(3):242-251. doi:10.1111/1346-8138.13243. PMID: 26945532

List of diseases covered by Hypotrichosis NGS panel

List of diseases covered by
Hermansky-Pudlak Syndrome NGS panel

Hermansky-Pudlak Syndrome NGS panel

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of Hermansky-Pudlak syndrome types
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling

Hermansky-Pudlak syndrome (HPS) is a group of rare hereditary disorders characterized by defective biogenesis of lysosome-related organelles. Clinical manifestations include oculocutaneous albinism, bleeding diathesis, and in some individuals pulmonary fibrosis, granulomatous colitis, immunodeficiency, or abnormal storage of fatty-like substance (ceroid lipofuscin) in various tissues of the body.

There are eleven different types of HPS, which can be stratified by their signs and symptoms and underlying genetic cause. Types 1 and 4 are the most severe forms of the disorder. Types 1, 2, and 4 are the only types associated with pulmonary fibrosis. Individuals with type 3, 5, or 6 have the mildest symptoms. Very few is known about the signs, symptoms, and severity of types 7, 8, 9, 10 and 11.

The test covers the known genetic causes of HPS. The disease is inherited in an autosomal recessive pattern.

HPS is a rare disorder in most populations and is estimated to affect 1: 500 000 to 1 000 000 individuals worldwide. Type 1 is more common in northwest Puerto Rico where about 1: 1800 people are affected. Type 3 is common in people from central Puerto Rico. Groups of affected individuals have been identified in many other regions, including India, Japan, the United Kingdom, and Western Europe. HPS is the third most prevalent form of albinism.

References:
Huizing M, Malicdan MCV, Gochuico BR, et al. Hermansky-Pudlak Syndrome. 2000 Jul 24 [Updated 2017 Oct 26]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. https://www.ncbi.nlm.nih.gov/books/NBK1287/. PMID:20301464
Huizing M, Malicdan MCV, Wang JA, et al. Hermansky-Pudlak syndrome: Mutation update. Hum Mutat. 2020;41(3):543-580. doi:10.1002/humu.23968. PMID:31898847
Merideth MA, Introne WJ, Wang JA, O’Brien KJ, Huizing M, Gochuico BR. Genetic variants associated with Hermansky-Pudlak syndrome. Platelets. 2020;31(4):544-547. doi:10.1080/09537104.2019.1663810. PMID:32436471
Pennamen P, Le L, Tingaud-Sequeira A, et al. BLOC1S5 pathogenic variants cause a new type of Hermansky-Pudlak syndrome [published online ahead of print, 2020 Jun 22]. Genet Med. 2020;10.1038/s41436-020-0867-5. doi:10.1038/s41436-020-0867-5. PMID:32565547

List of diseases covered by
Epidermolysis Bullosa NGS panel

Epidermolysis Bullosa NGS panel

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of epidermolysis bullosa types/subtypes and other genetically/
phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling

Inherited epidermolysis bullosa (EB) is a group of genetic diseases characterized by skin fragility and blistering on the skin and mucous membranes in response to minor injury or friction. EB is clinically and genetically very heterogeneous. There are four main types with additional sub-types identified and within each type, one may be either mildly or severely affected. Classification into four main types considers the layer of skin in which blistering occurs: EB simplex (intraepidermal), junctional EB (within the lamina lucida of the basement membrane), dystrophic EB (below the basement membrane), and Kindler EB (mixed skin cleavage pattern). Stratification of EB into several subtypes (up-to-date 34 subtypes in total) takes account the clinical characteristics, the pattern of genetic inheritance, the expression of the altered protein, and the genetic alteration. Pathogenic variants in at least 18 genes that encode proteins in the epidermis, basement membrane or dermis have been associated with different subtypes of EB. The characteristic phenotype of the different types of EB is correlated to the gene that is altered. In turn, different genes can lead to very similar EB phenotypes.

The test covers the known genetic causes of EB types/subtypes and a range of other genetically/phenotypically related disorders.

Depending on the type of EB it could be inherited in an autosomal dominant or autosomal recessive pattern.

The combined prevalence of all types of EB is estimated to be 11 per 1,000,000 individuals. EB simplex is estimated to be 6 per 1,000,000 people, junctional EB 0,5 per 1,000,000 people, dystrophic EB 3,3 per 1,000,000 people, and Kindler’s EB is reported in approximately 250 individuals worldwide.

References:
Mariath LM, Santin JT, Schuler-Faccini L, Kiszewski AE. Inherited epidermolysis bullosa: update on the clinical and genetic aspects [published online ahead of print, 2020 Jul 8]. An Bras Dermatol. 2020; S0365-0596(20)30171-9. doi:10.1016/j.abd.2020.05.001. PMID: 32732072
Pfendner EG, Bruckner AL. Epidermolysis Bullosa Simplex. 1998 Oct 7 [Updated 2016 Oct 13]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1369/
Pfendner EG, Lucky AW. Dystrophic Epidermolysis Bullosa. 2006 Aug 21 [Updated 2018 Sep 13]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1304/
Pfendner EG, Lucky AW. Junctional Epidermolysis Bullosa. 2008 Feb 22 [Updated 2018 Dec 20]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1125/
Pfendner EG, Lucky AW. Epidermolysis Bullosa with Pyloric Atresia. 2008 Feb 22 [Updated 2017 Sep 7]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1157/
Youssefian L, Vahidnezhad H, Uitto J. Kindler Syndrome. 2016 Mar 3 [Updated 2016 Dec 1]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK349072/

List of diseases covered by
Ehlers-Danlos Syndrome NGS panel

Ehlers-Danlos Syndrome NGS panel

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of Ehlers-Danlos syndrome types and other genetically/phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling

Ehlers-Danlos syndrome (EDS) is a group of rare disorders affecting connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. The 2017 classification describes 13 types of EDS. The symptoms depend upon the specific type of EDS. An unusually large range of joint movement occurs in most forms of EDS and many individuals with the EDS have soft, velvety skin that is highly stretchy (elastic) and fragile. The vascular type of disease causes bleeding problems, the cardiac-valvular type causes severe problems with the valves that control the movement of blood through the heart, and people with the kyphoscoliotic type experience severe curvature of the spine.

The test covers the known genetic causes of EDS types and a range of other genetically/phenotypically related disorders.

Depending on the type of EDS it could be inherited in an autosomal dominant or autosomal recessive pattern.

The combined prevalence of all types of EDS is estimated to affect 1 in 2500 to 5000 individuals in the general population. Most common are hypermobile and classical forms affecting 1 in 5,000 to 20,000 people and 1 in 20,000 to 40,000 people, respectively. Other forms of EDS are extremely rare.

References:

Byers PH. Vascular Ehlers-Danlos Syndrome. 1999 Sep 2 [Updated 2019 Feb 21]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1494/
Levy HP. Ehlers-Danlos Syndrome, Hypermobility Type. 2004 Oct 22 [updated 2016 Mar 31]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1279/
Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8-26. doi:10.1002/ajmg.c.31552. PMID: 28306229
Malfait F, Wenstrup R, De Paepe A. Ehlers-Danlos Syndrome, Classic Type. 2007 May 29 [updated 2011 Aug 18]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1244/
Pepin MG, Murray ML, Byers PH. Vascular Ehlers-Danlos Syndrome. 1999 Sep 2 [updated 2015 Nov 19]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1494/
Cannaerts E, Kempers M, Maugeri A, et al. Novel pathogenic SMAD2 variants in five families with arterial aneurysm and dissection: further delineation of the phenotype. J Med Genet. 2019;56(4):220-227. doi:10.1136/jmedgenet-2018-105304. PMID: 29967133

List of diseases covered by Cutis Laxa NGS panel

Cutis Laxa NGS panel

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of CL subtypes and other genetically/phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
4. Genetic counselling

Cutis laxa (CL) is a group of rare connective tissue disorders affecting the elastic fibers of the skin and characterized by loss of elasticity resulting in loosening, and wrinkling of the skin. Both congenital or acquired forms exist.

In inherited CL, an abnormal synthesis of extracellular matrix proteins occurs due to defects in genes coding for diverse extracellular matrix components. Besides skin anomalies, in most CL forms multiple organs are involved, leading to severe and in some forms even lethal multisystem disorders involving skeletal, cardiovascular, pulmonary, and central nervous systems. Different inborn errors of metabolism have been described with variable severity. Although the increasing number of CL-related diseases are described, a large part of the cases remain genetically unsolved.

The specific symptoms, severity and prognosis can vary greatly depending upon the specific type of CL and the presence and extent of associated symptoms. The considerable variability can occur even among individuals with the same subtype and even among members of the same family. In general, the autosomal recessive forms of CL tend to be more severe than the autosomal dominant forms.

The cutis laxa panel covers the most of the known genes related to inherited forms of CL subtypes and a range of disorders with CL symptoms. Currently, not all of the causative genes have been identified yet.

CL can be inherited in an autosomal dominant or autosomal recessive inheritance pattern.

CL affects males and females equally and individuals of all ethnic groups. The disorder has been reported in approximately 400 families worldwide. CL is estimated to affect 1 in 1,000,000 individuals in the general population. The adequate frequency of CL is difficult to estimate due to misdiagnosed or undiagnosed individuals.

References:
Callewaert BL, Urban Z. LTBP4-Related Cutis Laxa. 2016 Feb 11. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK343782/
Kaler SG. ATP7A-Related Copper Transport Disorders. 2003 May 9 [Updated 2016 Aug 18]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1413/
Loeys B, De Paepe A, Urban Z. EFEMP2-Related Cutis Laxa. 2011 May 12 [Updated 2015 Jul 23]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Table 2. [Disorders to Consider in the Differential Diagnosis of Cutis Laxa]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK54467/table/efemp2-cutis-laxa.T.disorders_to_conside/
Mohamed M, Voet M, Gardeitchik T, Morava E. Cutis Laxa. Adv Exp Med Biol. 2014;802:161-184. doi:10.1007/978-94-007-7893-1_11. PMID: 24443027
Mohamed M, Kouwenberg D, Gardeitchik T, Kornak U, Wevers RA, Morava E. Metabolic cutis laxa syndromes. J Inherit Metab Dis. 2011;34(4):907-916. doi:10.1007/s10545-011-9305-9. PMID: 21431621
Ritelli M, Cammarata‐ Scalisi F, Cinquina V, Colombi M. Clinical and molecular characterization of an 18‐month‐old infant with autosomal recessive cutis laxa type 1C due to a novel LTBP4 pathogenic variant, and literature review. Mol Genet Genomic Med . 2019;7:e735. https ://doi.org/10.1002/mgg3.735. PMID: 31115174
Van Maldergem L, Dobyns W, Kornak U. ATP6V0A2-Related Cutis Laxa. 2009 Mar 19 [Updated 2015 Feb 12]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK5200/
Van Maldergem L, Loeys B. FBLN5-Related Cutis Laxa. 2009 Mar 19 [Updated 2018 Aug 16]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK5201/

Congenital Myasthenic Syndrome NGS panel

List of diseases covered by
Congenital Myasthenic Syndrome NGS panel

List of diseases covered by
Coagulation Disorders NGS panel

Coagulation Disorders NGS panel

Von Hippel-Lindau Disease
VHL gene sequencing

Frazer Syndrome NGS panel

List of diseases covered by
Osteogenesis Imperfecta NGS panel

Osteogenesis Imperfecta NGS panel

Primary Ciliary Dyskinesia NGS panel

 

List of diseases covered by
Primary Ciliary Dyskinesia NGS panel

List of diseases covered by
Senior-Loken Syndrome NGS panel

Senior-Loken Syndrome NGS panel

Ehlers-Danlos Syndrome NGS panel

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of Ehlers-Danlos syndrome types and other genetically/phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling

Ehlers-Danlos syndrome (EDS) is a group of rare disorders affecting connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. The 2017 classification describes 13 types of EDS. The symptoms depend upon the specific type of EDS. An unusually large range of joint movement occurs in most forms of EDS and many individuals with the EDS have soft, velvety skin that is highly stretchy (elastic) and fragile. The vascular type of disease causes bleeding problems, the cardiac-valvular type causes severe problems with the valves that control the movement of blood through the heart, and people with the kyphoscoliotic type experience severe curvature of the spine.

The test covers the known genetic causes of EDS types and a range of other genetically/phenotypically related disorders.

Depending on the type of EDS it could be inherited in an autosomal dominant or autosomal recessive pattern.

The combined prevalence of all types of EDS is estimated to affect 1 in 2500 to 5000 individuals in the general population. Most common are hypermobile and classical forms affecting 1 in 5,000 to 20,000 people and 1 in 20,000 to 40,000 people, respectively. Other forms of EDS are extremely rare.

References:

Byers PH. Vascular Ehlers-Danlos Syndrome. 1999 Sep 2 [Updated 2019 Feb 21]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1494/
Levy HP. Ehlers-Danlos Syndrome, Hypermobility Type. 2004 Oct 22 [updated 2016 Mar 31]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1279/
Malfait F, Francomano C, Byers P, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8-26. doi:10.1002/ajmg.c.31552. PMID: 28306229
Malfait F, Wenstrup R, De Paepe A. Ehlers-Danlos Syndrome, Classic Type. 2007 May 29 [updated 2011 Aug 18]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1244/
Pepin MG, Murray ML, Byers PH. Vascular Ehlers-Danlos Syndrome. 1999 Sep 2 [updated 2015 Nov 19]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1494/
Cannaerts E, Kempers M, Maugeri A, et al. Novel pathogenic SMAD2 variants in five families with arterial aneurysm and dissection: further delineation of the phenotype. J Med Genet. 2019;56(4):220-227. doi:10.1136/jmedgenet-2018-105304. PMID: 29967133

Leukodystrophy and Leukoencephalopathy
NGS panel

Deletion/duplication analysis

List of diseases covered by AMD NGS panel

Thrombocytopenia NGS panel

Alpha Thalassemia
Deletion/duplication analysis

Beta Thalassemia
Sequencing of the HBB gene

Deletion/duplication analysis of the HBB gene

Fanconi Anemia
NGS panel

Deletion/duplication analysis

Noonan Spectrum Disorders/Rasopathies NGS panel

Deletion/duplication analysis of selected regions

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Parental testing in case of a causative mutation has been identified in an affected  individual
3. Genetic counseling
4. Prenatal diagnosis

Age-Related Macular Degeneration
Targeted mutation analysis

Indications for genetic testing:
1. Risk determination of at-risk individuals for early diagnosis and prediction of disease progression
2. Risk assessment of individuals with family history of AMD
3. Genetic counseling

Age-related macular degeneration (AMD) is characterized by pathological changes of the retinal pigment epithelium (RPE), progressive degeneration of photoreceptors, thickened Bruch’s membrane and choroidal neovascularization. These alterations lead to the loss of sharp, central vision. It is an age-related process and usually develops after a person reaches 50 years.
In Western Europe and USA 30% of people older than 75 years suffer from different types of AMD. 85-90% cases of AMD are dry AMD, which have no treatment. 10-15% cases of AMD are wet AMD, which have number of treatments available (injection into the eye to stop further development) and early diagnosis can save vision.
AMD increased risk assessment enables prevention and early diagnosis of the disease. The early diagnosis is vital to delay progression of disease and vision loss.