Ashkenazi Jewish diseases

Ashkenazi Jewish Diseases NGS panel

Genes
(full coding
region):
ABCC8, AGL, ASPA, BCKDHB, BLM, BRCA1, BRCA2, CFTR, CLRN1, DLD, F11, FANCC, FKTN, GBA, GJB2, G6PC, HEXA, IKBKAP, LCA5, LDLR, LRRK2, MCOLN1, MEFV, MSH2, MSH6, NEB, PCDH15, SERPINA1, SMN1, SMPD1, TMEM216, TOR1A

List of diseases covered by the panel


Lab method: NGS panel with CNV analysis

TAT: 6-9 weeks

Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.


Ordering information: Go to online ordering or download sample submission form

Indications for genetic testing:

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

In the Ashkenazi Jewish population, some severe and lethal genetic conditions occur with relatively high frequency. Current testing enables the analysis of the genes associated with  the following disorders in the Ashkenazi Jewish population: alpha 1-anti-trypsin deficiency, autosomal recessive retinitis pigmentosa,  Bardet-Biedl syndrome, Bloom syndrome, breast- and ovarian cancer, Canavan disease, cystic fibrosis, factor XI deficiency, familial dysautonomia,  familial hypercholesterolemia, familial hyperinsulinemia, familial mediterranean fever, Fanconi anemia, Gaucher disease, glycogen storage disease type 1A and IIIA,   Joubert syndrome II, Leber congenital amaurosis, lipoamide dehydrogenase deficiency, maple syrup urine disease, mucolipidosis type IV,  nemaline myopathy, Niemann-Pick A, non-syndromic sensorineural hearing loss, Tay-Sachs disease, Torsion dystonia, Usher syndrome type 1F and IIIA.

 

Cystic Fibrosis

Cystic Fibrosis
Sequencing of the CFTR gene

Genes
(full coding
region):
CFTR

Lab method: NGS. Deletions CFTRdele2,3, CFTRdele21, 1949del84 are included in the testing. Other large deletions and duplications of the CFTR gene will not be identified.

TAT: 4-6 weeks

Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.


Ordering information: Go to online ordering or download sample submission form

Deletion/duplication analysis of the CFTR gene

Genes: CFTR

Lab method: MLPA

TAT: 4-6 weeks

Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.


Ordering information: Go to online ordering or download sample submission form

Indications for genetic testing:

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

Cystic fibrosis (CF) is an autosomal recessive, multisystem disease. CF is characterized by recurrent lung infections, malabsorption, malnutrition, and male infertility. Cystic fibrosis is caused by thick and sticky mucus due to disturbances of salt homeostasis in cells.

CF is caused by mutations in the CFTR gene encoding cystic fibrosis transmembrane conductance regulator protein. The CFTR protein functions as a chloride channel expressed on epithelial cell membranes and controls the regulation of other transport pathways.

Cystic Fibrosis read more

Cystic Fibrosis

Cystic fibrosis (CF; OMIM®: 219700) is autosomal recessive, multisystem disease leading to significant morbidity and early death. Characteristic manifestations include recurrent lung infections, malabsorption, malnutrition, and infertility (especially in males). Cystic Fibrosis is caused by thick and sticky mucus due to the disturbances of salt homeostasis in cells. Biochemical hallmark of the disease is elevated sweat chloride concentration.

CF is caused by mutations in the cystic fibrosis conductance regulator gene (CFTR; OMIM®: *602421; HGNC number: 1884), located on chromosome 7. CFTR functions as a chloride channel and controls the regulation of other transport pathways. Asymptomatic carrier parents, who have no physiological or biochemical outcome that enables routine identification, typically have one CFTR mutation; whereas diseased progeny carry at least two mutations, one on each CFTR gene allele. CF has a high incidence in people of Northern European descent, occurring in approximately 1 in 2500 live births.

The most common mutant allele is the F508del mutation [1], which is a deletion of three basepairs at the 508th codon causing the deletion of a phenylalanine residue and subsequent defective intracellular processing of the CFTR protein that is an important chloride channel. Worldwide, the F508del mutation is responsible for approximately two-thirds (66%) of all CF chromosomes; however, there is great mutational heterogeneity in the remaining one-third of all alleles [2]. The next most frequent mutation was G542TER – a G-to-T change in nucleotide 1756 in exon 11 is responsible for a stop mutation in codon 542 [3].

Not only is there heterogeneity in the mutations causing Cystic Fibrosis, but the pathogenetic mechanisms also vary. Deletion of phenylalanine-508 appears to cause disease by abrogating normal biosynthetic processing and thereby resulting in retention and degradation of the mutant protein within the endoplasmic reticulum. Other mutations, such as the relatively common G551D mutation [4], appear to be normally processed and, therefore, must cause disease through some other mechanism. G551D mutation, which is within the first nucleotide-binding fold of the CFTR, is the third most common CF mutation, with a worldwide frequency of 3.1% among CF chromosomes [5]. Several mutations result in proteins that are too short because production is ended prematurely. Less common mutations produce proteins that do not use energy normally, do not allow chloride to cross the membrane appropriately, or are degraded at a faster rate than normal. Mutations may also lead to fewer copies of the CFTR protein being produced [6].

References:
[1]    Kerem B, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, Chakravarti A, Buchwald M, Tsui LC: Identification of the cystic fibrosis gene: genetic analysis. Science 1989, 245:1073-1080.
[2]    Bobadilla JM, Macek M Jr, Fine JP, Farrell JP: Cystic fibrosis: A worldwide analysis of CFTR mutations – correlation with incidence data and application to screening. Human Mutation 2002, 19 (6): 575-606.
[3]    Kerem B, Zielenski J, Markiewicz D, Bozon D, Gazit E, Yahav J, Kennedy D, Riordan JR, Collins FS, Rommens JM, Tsui L-C: Identification of mutations in regions corresponding to the 2 putative nucleotide (ATP)-binding folds of the cystic fibrosis gene. Proc. Nat. Acad. Sci. 1990, 87: 8447-8451.
[4]    Cutting GR, Kasch LM, Rosenstein BJ, Tsui L-C, Kazazian HH Jr, Antonarakis SE: Two patients with cystic fibrosis, nonsense mutations in each cystic fibrosis gene, and mild pulmonary disease. New Eng. J. Med. 1990, 323: 1685-1689.
[5]    Hamosh A, King TM, Rosenstein BJ, Corey M, Levison H, Durie P, Tsui L-C, McIntosh I, Keston M, Brock DJH, Macek M Jr, Zemkova D and 20 others: Cystic fibrosis patients bearing both the common missense mutation gly-to-asp at codon 551 and the delta-F508 mutation are clinically indistinguishable from delta-F508 homozygotes, except for decreased risk of meconium ileus. Am. J. Hum. Genet. 1992, 51: 245-250.
[6]    Rowe SM, Miller S, Sorscher EJ: “Cystic fibrosis”. N. Engl. J. Med. 2005, 352 (19): 1992–2001.

Asper Reprogenetics

Asper Reprogenetics

Ashkenazi Jewish Diseases
Carrier Testing
Cystic Fibrosis
Female Infertility UPDATED
Folate-Dependent Neural Tube Defects
Fragile X Syndrome
Male Factor Infertility UPDATED
Maternal Cell Contamination
Primary Ciliary Dyskinesia
Whole Exome Sequencing

Asper Reprogenetics comprises tests to determine carrier status of severe genetic diseases. Carrier testing is useful for individuals with family history of a genetic disorder and for people in certain ethnic groups with an increased risk of genetic conditions. The testing provides physicians and their patients valuable information for making calculated decisions regarding family planning and condition management.

Tests related to reproductive problems are also included in this testing selection. There are two main purposes of genetic testing – the identification of the infertility causes and optimization of the assisted reproductive technology. Genetic testing can play significant role in improving the reproductive outcomes of infertile couples. Moreover, couples would benefit from more fully informed decisions.