Ashkenazi Jewish Genetic Diseases Panel

  • 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
  • Carrier screening for expectant individuals and those planning a pregnancy AND diagnostic testing for individuals with symptoms of classic CF
  • Not included in prenatal screening panel for individuals of Ashkenazi Jewish descent

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 165 Pathogenic Variants 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)
    • ACMG for nine of the disorders described in the ACOG guidelines 
  • 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%

Clinical Sensitivity for Individuals of Ashkenazi Jewish Descent
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 (IKBKAP)

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 Testing 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
  1. GeneReviews - Gaucher Disease

    Pastores GM, Hughes DA. Gaucher Disease. In: Adam MP, Ardinger HH, Pagon RA, et al, editors. GeneReviews, University of Washington; 1993-2020. [Last Update: Jun 2018; Accessed: Feb 2020]

    Online
  2. GeneReviews - Fanconi Anemia

    Mehta PA, Tolar J. Fanconi Anemia. In: Adam MP, Ardinger HH, Pagon RA, et al, editors. GeneReviews, University of Washington; 1993-2020. [Last Revision: Mar 2018; Accessed: Feb 2020]

    Online
  3. GeneReviews - Bloom Syndrome

    Flanagan M, Cunniff CM. Bloom Syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al, editors. GeneReviews, University of Washington; 1993-2020. [Last Update: Feb 2019; Accessed: Feb 2020]

    Online