Asper Biogene – genetic testing company

Congenital Adrenal Hyperplasia
Sequencing of the CYP21A2 gene

Deletion/duplication analysis of the CYP21A2 gene

Limb-Girdle Muscular Dystrophy
NGS panel

Deletion/duplication analysis

Tuberous Sclerosis
NGS panel

Deletion/duplication analysis

Leukodystrophy and Leukoencephalopathy
NGS panel

Deletion/duplication analysis

Congenital Myopathy and Distal Myopathy
NGS panel

Deletion/duplication analysis 

Urea Cycle Disorder
NGS panel

Deletion/duplication analysis of the OTC gene

Porphyria
NGS panel

Deletion/duplication analysis

Methylmalonic Aciduria and Homocystinuria
NGS panel

Deletion/duplication analysis

Lysosomal Storage Disease
NGS panel

Deletion/duplication analysis

Fatty Acid Oxidation Disorder
NGS panel

Deletion/duplication analysis

Familial Lipoprotein Lipase Deficiency
Sequencing of the LPL gene

Deletion/duplication analysis of the LPL gene

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Differential diagnosis
3. Carrier testing for at-risk relatives
4. Genetic counseling

Familial lipoprotein lipase (LPL) deficiency is characterized by very severe hypertriglyceridemia with episodes of abdominal pain, recurrent acute pancreatitis, eruptive cutaneous xanthomata, and hepatosplenomegaly. Symptoms of the disease typically develop in childhood.

Familial LPL deficiency is inherited in an autosomal recessive manner. Mutations in the LPL gene cause the disease.

The prevalence of familial LPL deficiency is approximately one in 1,000,000 worldwide.

References:
Burnett JR et al 1999. Familial Lipoprotein Lipase Deficiency. GeneReviews®. Last Update: June 22, 2017.
Viljoen A, Wierzbicki AS. Diagnosis and treatment of severe hypertriglyceridemia. Expert Rev Cardiovasc Ther. 2012;10:505–14.

Dilated Cardiomyopathy
NGS panel

Deletion/duplication analysis

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis
3. Testing for at-risk family members
4. Genetic counseling

Dilated cardiomyopathy (DCM) is a progressive disease of heart muscle that is characterized by left ventricular enlargement and systolic dysfunction. Persons with DCM may be asymptomatic for a number of years. Complications usually occur later in the disease course and may include heart failure, arrhythmias, thromboembolic disease.

The disease initially manifests in adults in the fourth to sixth decade, it may also present at any age.

DCM can be categorized as acquired, syndromic, or nonsyndromic. DCM can be inherited in an autosomal dominant or X-linked manner. Most cases are inherited in an autosomal dominant manner.

References:
Hershberger RE, Morales A. Dilated Cardiomyopathy Overview. GeneReviews® Initial Posting: July 27, 2007; Last Update: August 23, 2018.
Judge, D. P. 2009. Use of Genetics in the Clinical Evaluation of Cardiomyopathy. JAMA, 302(22), 2471.doi:10.1001/jama.2009.1787 

Melanoma
NGS panel

Del/dup analysis

Androgen Insensitivity Syndrome
Sequencing of the AR gene

Deletion/duplication analysis of the AR gene

Arrhythmogenic Right Ventricular Dysplasia/
Cardiomyopathy
NGS panel

Deletion/duplication analysis

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Testing patients with arrhythmia with nonspecific cardiomyopathy
3. Risk assessment in relatives
4. Prenatal diagnosis for known familial mutation
5. Genetic counseling

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive fibrofatty replacement of the myocardium that predisposes to ventricular tachycardia and sudden death in young individuals and athletes. ARVC affects the right ventricle and in some cases also the left ventricle. The most common presenting symptoms are heart palpitations, syncope, and sudden death.

The presentation of disease is highly variable, and some affected individuals may not meet established clinical criteria. The mean age at diagnosis is 31 years.

ARVC is typically inherited in an autosomal dominant manner.

References:

Fontaine G et al. Arrhythmogenic right ventricular cardiomyopathies: clinical forms and main differential diagnoses. Circulation. 1998;97:1532–5. 
McNally E et al. Arrhythmogenic Right Ventricular Cardiomyopathy. GeneReviews Initial Posting: April 18, 2005; Last Update: May 25, 2017.

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

Craniosynostosis
NGS panel

Deletion/duplication analysis

Skeletal Dysplasia
NGS panel

Deletion/duplication analysis

Deletion/duplication analysis of selected regions

Thyroid Cancer
NGS panel

Del/dup analysis

Fanconi Anemia
NGS panel

Del/dup analysis

Pulmonary Arterial Hypertension
NGS panel

Deletion/duplication analysis

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis
3. Testing at-risk family members
4. Genetic counseling

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disorder caused by cellular proliferation and fibrosis of the small pulmonary arteries, which results in a progressive rise in pulmonary vascular resistance. Initial symptoms include dyspnea, fatigue, syncope, chest pain, palpitations and leg edema. The mean age at diagnosis is 36 years.

Although the pathogenesis of PAH begins in the pulmonary circulation, right heart failure is the major cause of morbidity and mortality.

PAH can be idiopathic (defined by absence of an underlying risk factor), heritable, induced by drugs or toxins, or associated with conditions such as connective tissue disease, congenital heart disease, portal hypertension, HIV infection, or schistosomiasis.

Hereditary PAH is inherited in an autosomal dominant manner. BMPR2 mutations remain the most common genetic cause of PAH, accounting for ~80% of hereditary PAH and ~20% idiopathic PAH. Pathogenic variants in other genes are less common (1%-3%).

References:
Austin ED et al 2002. Heritable Pulmonary Arterial Hypertension. GeneReviews®
Humbert M et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 43, 13S–24S (2004).
Simonneau G et al. 2013. Updated clinical classification of pulmonary hypertension. J. Am. Coll. Cardiol. 62, D34–D41 (2013).
Tielemans B et al 2019. TGFβ and BMPRII signalling pathways in the pathogenesis of pulmonary arterial hypertension. Drug Discov Today. 2019 Mar; 24(3):703-716.
Tonelli A R et al.2013. Causes and circumstances of death in pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 188, 365–369 (2013).

Neurodegeneration with Brain Iron Accumulation
NGS panel

Deletion/duplication analysis

Epilepsy
NGS panel

Deletion/duplication analysis

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Testing of at risk family members for known mutations
3. Prenatal diagnosis for known familial mutations
4. Genetic counseling

Epilepsy is a clinically and genetically heterogeneous group of disorders characterized by epileptic seizures and other symptoms of neurological problems. Epilepsy can be caused by strokes, brain tumors, head injuries, structural brain abnormalities, brain infections and genetic syndromes.

The epilepsies can be classified into three classes: genetic generalized, focal and encephalopathic epilepsies, with several specific disorders within each class. The genetic generalized epilepsy syndromes include juvenile myoclonic epilepsy and childhood absence epilepsy among others. Focal epilepsy syndromes include temporal lobe epilepsy, autosomal dominant nocturnal frontal lobe epilepsy and autosomal dominant epilepsy with auditory features. Epileptic encephalopathies are severe, early onset conditions characterized by refractory seizures, developmental delay or regression associated with ongoing epileptic activity, and generally poor prognosis.

Epilepsy is often a concurrent condition in individuals with intellectual disability, autism or schizophrenia.

Genetic factors are relevant in the development of epilepsy. Most genes being implicated in epilepsy are involved in dysfunction or dysregulation of ion channels.

References:

Chang BS, Lowenstein DH (2003). “Epilepsy”. N. Engl. J. Med. 349 (13): 1257–66.
Hildebrand MS et al. Recent advances in the molecular genetics of epilepsy. J Med Genet. 2013;50:271–9.
Myers CT and Mefford hC. Advancing epilepsy genetics in the genomic era. Genome Medicine2015 7:91 

Retinoblastoma
Sequencing of the RB1 gene

Deletion/duplication analysis of the RB1 gene

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Testing of at-risk family members of an affected individual
4. Genetic counseling
5. Prenatal diagnosis for known familial mutation

Retinoblastoma is a malignant tumor of the developing retina that affects children, usually before the age of 5. The most common sign of retinoblastoma is a white pupillary reflex (leukocoria). Other symptoms may include strabismus, change in eye appearance, reduced visual acuity. Retinoblastoma may be unifocal or multifocal. About 60% of affected individuals have unilateral retinoblastoma, about 40% have bilateral retinoblastoma.

Hereditary retinoblastoma is inherited in an autosomal dominant pattern. Individuals with heritable retinoblastoma have a higher risk of developing non-ocular tumors.

The estimated incidence of retinoblastoma is 1 in 15 000 – 20 000 live births.

References:

Lohmann DR and Gallie BL. Retinoblastoma. GeneReviews® 2000 July 18 (Updated 2015 November 19)
Genetics Home Reference https://ghr.nlm.nih.gov.
Seregard S, et al. Incidence of retinoblastoma from 1958 to 1998 in Northern Europe: advantages of birth cohort analysis. Ophthalmology. 2004;111:1228–32.

Dystonia
NGS panel

Deletion/duplication analysis

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Carrier testing for at-risk relatives
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing repetitive movements and/or abnormal postures. Dystonic movements are typically patterned and twisting, affecting the neck, torso, limbs, eyes, face, vocal chords, and/or a combination of these muscle groups. The movements may be associated with tremor.

There are a number of different forms of dystonia, and many diseases are associated with the condition. Dystonia can be classified clinically and/or etiologically by anatomic changes (nervous system pathology) and causation (inherited, acquired, or idiopathic). Classifying dystonia by clinical features includes age of onset, body distribution, temporal pattern, and associated features.

Hereditary dystonias are usually inherited in an autosomal dominant manner and less commonly in an autosomal recessive or X-linked manner.

References:

Albanese A et al. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013;28:863–73.
Klein C et al. Dystonia Overview. GeneReviews® 2003 Oct 28 (Updated 2014 May 1).
Koc F and Yerdelen D. Metformin-induced paroxysmal dystonia. Neurosciences (Riyadh). 2008 Apr;13(2):194-5.

Parkinson’s Disease
NGS panel

Deletion/duplication analysis

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Determination of differential diagnosis
3. Genetic counseling

Parkinson’s disease (PD) is a progressive neurodegenerative disorder mainly affecting the motor system. PD is characterized by tremor, rigidity, bradykinesia, poor balance, and difficulty with walking. Non-motor findings include insomnia, depression, anxiety, behavioral problems, at a later stage of the disease psychosis and dementia may occur.

PD is most commonly a non-Mendelian disorder resulting from the effects of multiple genes as well as environmental risk factors. Mendelian forms of PD are inherited in an autosomal dominant, autosomal recessive, or, rarely, X-linked manner. The most common sporadic form of PD manifests around age 60, however, young-onset and juvenile-onset are seen.

References:

Davie CA. A review of Parkinson’s disease. 2008. Br. Med. Bull. 86 (1): 109–27.
Farlow J et al. Parkinson Disease Overview. GeneReviews® 2004 May 25 (Updated 2014 Feb 27).

Frontotemporal Dementia
NGS panel

Deletion/duplication analysis

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Determination of differential diagnosis
3. Testing of at-risk asymptomatic adults
4. Genetic counseling

Frontotemporal dementia (FTD) is a degenerative condition characterized by progressive neuronal loss in the temporal and frontal lobes of the brain. Clinical presentations may include behavioral changes, language disturbances, aphasia, extrapyramidal signs, rigidity, bradykinesia, supranuclear palsy, saccadic eye movement disorders, and mutism.

FTD usually occurs between ages 40 and 60 years, but may appear earlier or later. Most individuals diagnosed with the disorder have had an affected parent with the clinical symptoms of frontotemporal dementia. FTD is inherited in an autosomal dominant manner.

References:

Cardarelli R et al. Frontotemporal dementia: a review for primary care physicians. Am Fam Physician. 2010 Dec 1;82(11):1372-7.
Harms MM et al. TARDBP-Related Amyotrophic Lateral Sclerosis. GeneReviews® 2009 April 23 (Updated 2015 March 12).
Hsiung G-YR and Feldman HH. GRN-Related Frontotemporal Dementia. GeneReviews® 2007 Sept 7 (Updated 2013 March 14).
Van Swieten JC et al. MAPT-Related Disorders. GeneReviews® 2000 Nov 7 (Updated 2010 Oct 26).

Hypertrophic Cardiomyopathy
NGS panel

Deletion/duplication analysis

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Determination of differential diagnosis
3. Testing of at-risk family members
4. Genetic counseling

Hypertrophic cardiomyopathy (HCM) is typically defined by the presence of left ventricular hypertrophy (LVH) that is not solely explained by abnormal loading conditions. HCM is a significant cause of sudden cardiac death in competitive athletes. The clinical features of HCM are highly variable ranging from asymptomatic LVH to arrhythmias, to refractory heart failure. The symptoms include shortness of breath, orthostasis, presyncope, syncope, palpitations, and chest pain.

The prevalence in the general population is estimated at 1/500.

HCM is most commonly caused by mutations in one of the genes that encode different components of the sarcomere and is inherited in an autosomal dominant manner. In 3–5% of the cases affected individuals carry two mutations in the same gene (compound heterozygous or homozygous), or in different genes (digenic). This is associated with a more severe phenotype with younger age of onset and more adverse events.

References:

Cirino AL and Ho C. Hypertrophic Cardiomyopathy Overview. GeneReviews®. 2008 August 5 (Updated 2014 Jan 16) 
Elliott PM et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy. European Heart Journal (2014) 35, 2733–2779.
Maron BJ. Sudden death in young athletes. N Engl J Med. 2003;349:1064–75.
Richard P et al. Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation 2003; 107: 2227–2232.
Richard P et al. Homozygotes for a R869G mutation in the beta-myosin heavy chain gene have a severe form of familial hypertrophic cardiomyopathy. J Mol Cell Cardiol 2000; 32: 1575–1583.

Hereditary Spastic Paraplegia NGS panel

Targeted mutation analysis

Deletion/duplication analysis

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Determination of differential diagnosis
3. Carrier status detection of known mutation
4. Prenatal diagnosis for known familial mutation
5. Genetic counseling

Hereditary Spastic Paraplegia (HSP) is a group of clinically and genetically heterogeneous disorders characterized by lower extremity spasticity and weakness.

HSP is classified as uncomplicated, or pure, when only spinal involvement occurs, and is classified as complicated when accompanied by other system involvement or other neurologic findings such as ataxia, seizures, intellectual disability, dementia, amyotrophy, extrapyramidal disturbance, or peripheral neuropathy.

HSP can be inherited in an autosomal dominant, autosomal recessive, x-linked recessive or maternally inherited (mitochondrial) manner.

The prevalence of all hereditary spastic paraplegias is estimated to be 2 to 6 in 100,000 people worldwide.

References:

Fink JK. Hereditary Spastic Paraplegia Overview. GeneReviews® 2000 Aug 15 (Updated 2014 Feb 6)
National Institute of Health 2008. Hereditary Spastic Paraplegia Information Page.
Sawhney IM, Bansal SK, Upadhyay PK, et al. Evoked potentials in hereditary spastic paraplegia. Ital J Neurol Sci. 1993 Sep. 14(6):425-8.

Usher Syndrome
NGS panel

Targeted regions sequencing

Deletion/duplication analysis

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Carrier testing for at-risk family members
3. Genetic counseling
4. Prenatal diagnosis for known familial mutation

Usher syndrome is a combination of retinitis pigmentosa and sensorineural hearing loss with or without vestibular dysfunction. Usher syndrome represents 50% of all cases with deafness and blindness. Usher syndrome is inherited in an autosomal recessive manner. Three major clinical types can be distinguished. Usher syndrome type I (USH1) is characterized by severe to profound congenital hearing loss, RP and vestibular areflexia. Patients with Usher syndrome type II (USH2) have moderate to severe hearing loss, RP and normal or variable vestibular function. Patients with Usher syndrome type III (USH3) have progressive hearing loss, RP and variable vestibular function.

Waardenburg Syndrome
NGS panel

Deletion/duplication analysis

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Carrier testing for at-risk relatives
3. Genetic counseling

Waardenburg syndrome (WS) is a group of genetic conditions characterized by sensorineural hearing loss and pigmentary abnormalities of the iris, hair, and skin, along with dystopia canthorum. Hearing loss is congenital, typically non-progressive, either unilateral or bilateral, and sensorineural.

The classic sign of hair pigmentation anomaly with WS is white forelock appearing typically in the teen years. Ocular pigmentary manifestations may include complete or segmental heterochromia or hypoplastic or brilliant blue irides.

Waardenburg syndrome affects an estimated 1 in 20,000-40,000 people.

Four types of WS can be distinguished by physical characteristics and genetic cause. Types I and III are inherited in an autosomal dominant manner, types II and IV are autosomal recessive.

References:

Farrer LA et al. Waardenburg syndrome (WS) type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: first report of the WS consortium. Am J Hum Genet. 1992;50:902–13.
Milunsky JM. Waardenburg Syndrome Type I. GeneReviews® 2001 July 30 (Updated 2014 Aug 7)
Shields CL et al. Waardenburg syndrome: iris and choroidal hypopigmentation: findings on anterior and posterior segment imaging. JAMA Ophthalmol. 2013;131:1167–73.
Tamayo ML et al. Screening program for Waardenburg syndrome in Colombia: clinical definition and phenotypic variability. Am J Med Genet A. 2008;146A:1026–31.

Treacher Collins Syndrome
NGS panel

Deletion/duplication analysis of the TCOF1 gene

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Carrier testing for at-risk family members
3. Genetic counseling

Treacher Collins syndrome (TCS) is a congenital disorder characterized by craniofacial deformities, external ear abnormalities, and eye anomalies. The most characteristic features of TCS are micrognathia, conductive hearing loss, coloboma of the lower eyelid, and absence of the lower eyelashes. Less common signs include cleft palate and unilateral or bilateral choanal stenosis or atresia.

TCS affects an estimated 1 in 50,000 people. The disorder has an autosomal dominant pattern of inheritance. Approximately 1% of TCS is inherited in an autosomal recessive manner.

References:

Chiara C et al. Novel mutations of TCOF1 gene in European patients with treacher Collins syndrome. 2011. Medical Genetics 12.
Katsanis SH and Jabs EW. Treacher Collins Syndrome. GeneReviews®. 2004 July 20 (Updated 2012 Aug 30)
Trainor PA et al. Treacher Collins syndrome: etiology, pathogenesis and prevention. 2008. European Journal of Human Genetics 17 (3): 275–283.

Stickler Syndrome
NGS panel

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Carrier testing for at-risk family members
3. Genetic counseling

Stickler syndrome is a group of hereditary conditions affecting connective tissue. Stickler syndrome is characterized by ocular findings, distinctive facial abnormalities, hearing loss, skeletal abnormalities, and joint problems.

Eye findings may include high myopia, cataract, vitreoretinal or chorioretinal degeneration, and retinal detachment. Hearing loss can be both conductive and sensorineural. Affected individuals have a characteristic flattened facial appearance caused by midfacial underdevelopment and cleft palate.

Stickler syndrome is inherited in an autosomal dominant or autosomal recessive manner. Stickler syndrome affects approximately 7,500 to 9,000 newborns.

References:

Annunen S et al. Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes. 1999. Am J Hum Genet 65 (4): 974–83.
Printzlau A, Andersen M. Pierre Robin sequence in Denmark: a retrospective population-based epidemiological study. Cleft Palate Craniofac J. 2004;41:47–52.
Robin NH et al. Stickler Syndrome. GeneReviews® 2000 June 9 (Updated 2014 Nov 26)

Branchiootorenal Syndrome
NGS panel

Deletion/duplication analysis of the EYA1 gene

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Genetic counseling
3. Prenatal diagnosis for known familial mutation

Branchiootorenal (BOR) syndrome is characterized by malformations of the outer, middle, and inner ear associated with conductive, sensorineural, or mixed hearing impairment, branchial arch anomalies (branchial clefts, fistulae, cysts), and renal abnormalities. Renal malformations may include urinary tree malformation, renal hypoplasia or agenesis, renal dysplasia, renal cysts. In some cases, end-stage renal disease develops later in life.

BOR manifests wide clinical heterogeneity between affected individuals. Estimated prevalence of the disease is 1/40,000.

BOR syndrome is transmitted in an autosomal dominant manner.

References:

Fraser FC et al. Genetic aspects of the BOR syndrome—branchial fistulas, ear pits, hearing loss and renal anomalie. Am J Med Genet1978; 2: 241–252
Melnick M et al. Branchio‐oto‐renal dysplasia and branchio‐oto dysplasia: two distinct autosomal dominant disorders. Clin Genet1978; 13: 425–442
Smith RJH. Branchiootorenal Spectrum Disorders. GeneReviews® 1999 March 19 (Updated 2013 June 20)

Pendred Syndrome
Sequencing of the SLC26A4 gene

Deletion/duplication analysis of the SLC26A4 gene

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Carrier status detection of known mutation
3. Genetic counseling

Pendred syndrome is an autosomal recessive condition characterized by bilateral sensorineural hearing impairment, vestibular and cochlear abnormalities, temporal bone abnormalities and goiter. Considerable phenotypic variability is found even within the same family. Sensorineural hearing loss is usually congenital, severe to profound and non-progressive. However, hearing loss may be later onset and progressive in some patients.

Pendred syndrome, as well as nonsyndromic hearing loss and deafness (DFNB4) show similar phenotypic spectrum. DFNB4 is characterized by nonsyndromic sensorineural hearing loss, vestibular dysfunction, enlarged vestibular aqueduct but normal thyroid function.

For further information:

Alasti F et al. Pendred Syndrome/DFNB4. GeneReviews® 1998 Sept 28 (Updated 2014 May 29)
Napiontek U et al. Intrafamilial variability of the deafness and goiter phenotype in Pendred syndrome caused by a T416P mutation in the SLC26A4 gene. J Clin Endocrinol Metab. 2004;89:5347–51.
Reardon W, Trembath RC: Pendred syndrome. J Med Genet 1996; 33: 1037–40.
Stinckens C et al. Fluctuant, progressive hearing loss associated with Menière like vertigo in three patients with the Pendred syndrome. Int J Pediatr Otorhinolaryngol. 2001;61:207–15.

Alport Syndrome
NGS panel

Deletion/duplication analysis

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Carrier testing for at-risk relatives
3. Genetic counseling
4. Prenatal diagnosis for known familial mutation

Alport syndrome is characterized by renal, cochlear, and ocular involvement. The main manifestation is glomerular nephropathy with hematuria, progressing to end-stage renal disease. Eye abnormalities include anterior lenticonus, maculopathy, corneal endothelial vesicles, and recurrent corneal erosion. The hearing loss develops gradually and is usually detectable during late childhood or early adolescence.

Prevalence of Alport syndrome is estimated at 1/50 000.

Alport syndrome is caused by mutations in COL4A3, COL4A4, and COL4A5 genes. The disease is known to be inherited in an X-linked, autosomal recessive or autosomal dominant pattern.

References:

Clifford EK. Alport Syndrome and Thin Basement Membrane Nephropathy. GeneReviews® 2001 Aug 28 (Updated 2013 Feb 28)
Hertz JM et al. Clinical utility gene card for: Alport syndrome. European Journal of Human Genetics. 2012. 20 doi:10.1038/ejhg.2011.237 (Updated 2014 Nov 12)

Wilson Disease
Sequencing of the ATP7B gene

Deletion/duplication analysis of the ATP7B gene

p.H1069Q (c.3207C>A p.His1069Gln) gene mutation analysis

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Carrier testing for at-risk family members
3. Genetic counseling

Wilson disease (WD) is an autosomal recessive inherited disorder characterized by the toxic accumulation of copper in various organs including the liver, the cornea and the brain, causing damage therein. The disorder usually manifests in the second decade of life and the hepatic form usually appears earlier than the neurological form. Wilson disease is caused by mutations in the ATP7B gene.

Mitochondrial Diseases
Mitochondrial genome sequencing

Nuclear genes of NGS panel

Single gene sequencing

MELAS Syndrome targeted mutation analysis

Deletion/duplication analysis

Indications for genetic testing:

1. Diagnosis of patients with phenotype characteristic for mitochondrial disease
2. Diagnosis of patients with family history suggestive for mitochondrial disease
3. Genetic counseling of individuals with mitochondrial disease and affected family members

Mitochondrial diseases are a genetically and clinically heterogeneous group of disorders that arise as a consequence of dysfunction of the mitochondrial respiratory chain. The estimate for the prevalence of all mitochondrial disorders 1:8500, but they are thought to be greatly under-diagnosed. Mitochondrial disorders can be caused by mutations of nuclear or mitochondrial DNA (mtDNA). If nuclear gene defects may be inherited in an autosomal recessive or autosomal dominant manner, mtDNA defects are transmitted only maternally. As the female could have heteroplasmic mtDNA mutations, which could be transmitted unequally to her offspring, the sibs could exhibit considerable clinical variability.

Symptoms of the mitochondrial disease can begin at any age. Mitochondrial disorders may affect a single organ (e.g. Leber hereditary optic neuropathy, LHON) or involve multiple organ systems (e.g. Myoclonic epilepsy with ragged-red fibers, MERRF). Common clinical features of mitochondrial disorder include, for example muscle weakness, exercise intolerance, trouble with balance and coordination, sensorineural deafness, impaired vision, seizures and learning deficits, cardiomyopathy, diabetes mellitus, stunted growth, and a high incidence of mid- and late pregnancy loss.

References:

Wallace DC. Mitochondrial diseases in man and mouse. Science. 1999;283:1482–8.
Chinnery PF. Mitochondrial Disorders Overview. Pagon RA, Adam MP, Bird TD, et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2013.
DiMauro S, Schon EA. Nuclear power and mitochondrial disease. Nat Genet. 1998;19:214–5.
Leonard JV, Schapira AVH. Mitochondrial respiratory chain disorders I: mitochondrial DNA defects. Lancet. 2000a;355:299–304.
Leonard JV, Schapira AVH. Mitochondrial respiratory chain disorders II: neurodegenerative disorders and nuclear gene defects. Lancet. 2000b;355:389–94.