Asper Biogene – genetic testing company

Paroxysmal Dyskinesia NGS panel

Senior-Loken Syndrome NGS panel

List of diseases covered by
Polycystic Kidney Disease NGS panel

Polycystic Kidney Disease NGS panel

Nephrotic Syndrome NGS panel

List of diseases covered by
Nephronophthisis NGS panel

Ciliopathy NGS panel

Bardet-Biedl Syndrome NGS panel

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.

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 of the MLYCD gene

Lysosomal Storage Disease
NGS panel

Deletion/duplication analysis

Fatty Acid Oxidation Disorder
NGS panel

Deletion/duplication analysis of the SLC22A5 gene

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 Analysis

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 of the TWIST1 gene

Noonan Spectrum Disorders/Rasopathies NGS panel

Skeletal Dysplasia
NGS panel

Deletion/duplication analysis

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.