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FeedbackPolymerase Chain Reaction (PCR)/Fluorescence Monitoring
- Preferred gene panel for carrier screening for individuals of Ashkenazi Jewish descent considering pregnancy or currently pregnant
- Detect 51 variants associated with 16 disorders common in individuals of Ashkenazi Jewish descent
This panel does not include prenatal screening for cystic fibrosis; refer to the Cystic Fibrosis (CFTR) Expanded Variant Panel Test Fact Sheet for information on cystic fibrosis prenatal screening.
Individuals of Ashkenazi Jewish descent are at an increased risk for certain autosomal recessive genetic disorders. An estimated one in every four or five individuals of Ashkenazi Jewish descent is a carrier for one of these disorders.
In combination, the Ashkenazi Jewish Disease Panel and Cystic Fibrosis (CFTR) Expanded Variant Panel tests screen for all of the disorders that the American College of Medical Genetics and Genomics (ACMG) and the American College of Obstetrics and Gynecology (ACOG) recommend testing for in individuals of Ashkenazi Jewish descent.
Disease Overview
Screening
- Routine preconception or prenatal carrier screening for genetic diseases common in individuals of Ashkenazi Jewish descent is recommended by:
- ACOG
- ABCC8-related hyperinsulinemia
- Bloom syndrome
- Canavan disease
- Cystic fibrosis
- Fanconi anemia group C
- Familial dysautonomia
- Gaucher disease
- Glycogen storage disease type 1A
- Joubert syndrome type 2
- Maple syrup urine disease type 1B
- Mucolipidosis type IV
- Niemann-Pick type A
- Tay-Sachs disease
- Usher syndrome (type 1F and type 3)
- ACOG
- Screening for a specific disorder may be offered to individuals not of Ashkenazi Jewish descent, including:
- Relatives who carry one or more variants included in the test
- Reproductive partners who are carriers of one of the panel disorders, although detection rates for non-Ashkenazi individuals is variable by disorder and largely unknown
For additional clinical information and the carrier frequency of diseases included on the Ashkenazi Jewish Diseases, 16 Genes panel, see the Ashkenazi Jewish Genetic Diseases Consult topic.
Genetics
Inheritance
Autosomal recessive
Genes/Variants
See Clinical Sensitivity table
Test Interpretation
Analytical sensitivity/specificity: 99%
| Disease (and Associated Gene) | Variants Tested (HGVS Nomenclature) | Variants Tested (Legacy Nomenclature) | Clinical Sensitivity in Individuals of Ashkenazi Jewish Descent | Clinical Sensitivity in non-Ashkenazi Jewish Individuals | Carrier Risk After Negative Test for Ashkenazi Jewish Individuals |
|---|---|---|---|---|---|
| ABCC8-related hyperinsulinism (ABCC8) | p.F1388del (c.4163_4165del) p.V187D (c.560T>A) c.3992-9G>A | n/a | 97% | Unknown | 1/1,700 |
| Bloom syndrome (BLM) | p.Y736Lfs (c.2207_2212delinsTAGATTC) | 2281del6/ins7 | 97% | ~3% | 1/3,300 |
| Canavan disease (ASPA) | c.433-2A>G p.Y231X (c.693C>A) p.E285A (c.854A>C) p.A305E (c.914C>A) | n/a | 99% | 55% | 1/4,900 |
| Familial dysautonomia (ELP1) | p.R696P (c.2087G>C) c.2204+6T>C |
IVS20+6T>C | 99% | Unknown | 1/3,100 |
| Fanconi anemia group C (FANCC) | p.D23Ifs (c.67delG) c.456+4A>T | 322delG IVS4+4A>T | 99% | Unknown | 1/8,800 |
| Gaucher disease (GBA) | p.L29Afs (c.84dupG) c.115+1G>A p.N409S (c.1226A>G) c.1263_1317del55 p.V433L (c.1297G>T) p.D448H (c.1342G>C) p.L483P (c.1448T>C) p.R535H (c.1604G>A) | 84G>GG IVS2+1G>A N370S del55bp V394L D409H L444P R496H | 90% | 55% | 1/140 |
| Glycogen storage disease type 1A (G6PC) | p.Q27Rfs (c.79delC) p.Y128Tfs (c.379_380dupTA) p.R83H (c.248G>A) p.R83C (c.247C>T) p.G188R (c.562G>C) p.Q242X (c.724C>T) p.Q347X (c.1039C>T) p.G270V (c.809G>T) p.F327del (c.979_981delTTC) | n/a | 99% | Varies by ethnicity | 1/7,000 |
| Joubert syndrome type 2 (TMEM216) | p.R73L (c.218G>T) | n/a | 99% | Unknown | 1/9,100 |
| Lipoamide dehydrogenase deficiency (DLD) | p.Y35X (c.104dupA) p.G229C (c.685G>T) | n/a | 99% | Unknown | 1/9,300 |
| Maple syrup urine disease type 1B (BCKDHB) | p.R183P (c.548G>C) p.G278S (c.832G>A) p.E372X (c.1114G>T) | n/a | 99% | Unknown | 1/11,000 |
| Mucolipidosis type IV (MCOLN1) | c.406-2A>G g.511_6943del | IVS3-2A>G del6.4kb | 95% | 6-10% | 1/2,500 |
| NEB-related nemaline myopathy (NEB) | exon 55 del (p.R2478_D2512del) | n/a | 99% | Unknown | 1/10,700 |
| Niemann-Pick disease type A (SMPD1) | p.L304P (c.911T>C) p.F333Sfs (c.996delC) p.R498L (c.1493G>T) p.R610del (c.1829_1831delGCC) | L302P fsP330 R496L R608del | 90% | Varies by ethnicity | 1/900 |
| Tay-Sachs disease (HEXA)a | 7.6 kb del p.G269S (c.805G>A) c.1073+1G>A p.Y427Ifs (c.1274_1277dup TATC) c.1421+1G>C Pseudodeficiency alleles: p.R247W (c.739C>T) p.R249W (c.745C>T) | IVS9+1G>A 1278dupTATC IVS12+1G>C | 94% | 59% | 1/480 |
| Usher syndrome type 1F (PCDH15) | p.R245X (c.733C>T) | n/a | 62% | Unknown | 1/190 |
| Usher syndrome type 3 (CLRN1) | p.N48K (c.144T>G) | n/a | 98% , | Unknown | 1/7,000 |
aFor specific Tay-Sachs disease testing, see the Tay-Sachs Disease (HEXA) Sequencing and Deletion/DuplicationTest Fact Sheet. n/a, not applicable | |||||
Results
- Positive: one pathogenic variant detected
- Individual is a carrier of the associated disease
- Screening for that disease should be offered to the individual’s reproductive partner
- Genetic counseling is recommended
- Negative: no targeted pathogenic variants identified
- For residual carrier risk estimates, see the Clinical Sensitivity table
Limitations
- Variants other than those tested on this panel will not be detected
- Diagnostic errors can occur due to rare sequence variations
References
-
28225420
ACOG Committee on Genetics. Committee Opinion No. 690 Summary: Carrier screening in the age of genomic medicine. Obstet Gynecol. 2017;129(3):595-596.
-
28225426
ACOG Committee on Genetics. ACOG Committee Opinion No. 691: carrier screening for genetic conditions. Obstet Gynecol. 2017;129(3):e41-e55.
-
21716120
Glaser B, Blech I, Krakinovsky Y, et al. ABCC8 mutation allele frequency in the Ashkenazi Jewish population and risk of focal hyperinsulinemic hypoglycemia. Genet Med. 2011;13(10):891-894.
-
17407155
German J, Sanz MM, Ciocci S, et al. Syndrome-causing mutations of the BLM gene in persons in the Bloom's Syndrome Registry. Hum Mutat. 2007;28(8):743-753.
-
GeneReviews Canavan Disease - Jewish Genetic Dz
Matalon R, Delgado L, Michals-Matalon K. Canavan disease. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews. University of Washington, Seattle. Last update Sep 2018; accessed May 2020.
-
GeneReviews - Gaucher Disease
Pastores GM, Hughes DA. Gaucher disease. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews, University of Washington; 1993-2020. [Last Update: Jun 2018; Accessed: May 2020]
-
15316959
Ekstein J, Rubin BY, Anderson SL, et al. Mutation frequencies for glycogen storage disease Ia in the Ashkenazi Jewish population. Am J Med Genet A. 2004;129A(2):162-164.
-
20036350
Edvardson S, Shaag A, Zenvirt S, et al. Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation. Am J Hum Genet. 2010;86(1):93-97.
-
9934985
Shaag A, Saada A, Berger I, et al. Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews. Am J Med Genet. 1999;82(2):177-182.
-
11509994
Edelmann L, Wasserstein MP, Kornreich R, et al. Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population. Am J Hum Genet. 2001;69(4):863-868.
-
GeneReviews Mucolipidosis IV - Jewish Genetic Dz
Schiffmann R, Grishchuk Y, Goldin E. Mucolipidosis IV. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews. University of Washington, Seattle. Last update Jul 2015; accessed May 2020.
-
15221447
Anderson SL, Ekstein J, Donnelly MC, et al. Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene. Hum Genet. 2004;115(3):185-190.
-
GeneReviews Acid Sphingomyelinase Deficiency - Jewish Genetic Dz
Wasserstein MP, Schuchman EH. Acid sphingomyelinase deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews. University of Washington, Seattle. Last update Jun 2015; accessed May 2020.
-
8230592
Kaback M, Lim-Steele J, Dabholkar D, et al. Tay-Sachs disease--carrier screening, prenatal diagnosis, and the molecular era. An international perspective, 1970 to 1993. The International TSD Data Collection Network. JAMA. 1993;270(19):2307-2315.
-
12711741
Ben-Yosef T, Ness SL, Madeo AC, et al. A mutation of PCDH15 among Ashkenazi Jews with the type 1 Usher syndrome. N Engl J Med. 2003;348(17):1664-1670.
-
12145752
Fields RR, Zhou G, Huang D, et al. Usher syndrome type III: revised genomic structure of the USH3 gene and identification of novel mutations. Am J Hum Genet. 2002;71(3):607-617.
-
14569126
Ness SL, Ben-Yosef T, Bar-Lev A, et al. Genetic homogeneity and phenotypic variability among Ashkenazi Jews with Usher syndrome type III. J Med Genet. 2003;40(10):767-772.