Ashkenazi Jewish Genetic Diseases

  • Diagnosis
  • Algorithms
  • Screening
  • Background
  • Lab Tests
  • References
  • Related Topics
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Indications for Testing

  • Carrier screening for 16 disorders in individuals of Ashkenazi Jewish descent who are planning a pregnancy or are currently pregnant (see Screening section)
  • Panel testing is recommended for all individuals of Ashkenazi Jewish descent who are planning a pregnancy or are currently pregnant
  • Screening for a specific disorder may be offered to non-Ashkenazi Jews
    • With relatives who carry ≥1 variants included in the test
    • Whose partners are carriers of one of the panel disorders
      • Detection rate for non-Ashkenazi Jews is variable by disorder and largely unknown
      • Consider full gene sequencing or enzyme assay for those of non-Ashkenazi Jewish descent
  • For cystic fibrosis testing, see Cystic Fibrosis
  • The American College of Obstetrics and Gynecology (ACOG) and the American College of Medical Genetics (ACMG) recommend routine preconception or prenatal carrier screening for diseases common to individuals of Eastern European (Ashkenazi) Jewish descent
    • ACOG 2009 guidelines recommend screening for 4 disorders – Canavan disease, cystic fibrosis, familial dysautonomia, and Tay-Sachs disease
      • ACOG states that individuals of Ashkenazi Jewish descent may inquire about the availability of carrier screening for other disorders
    • ACMG 2008 guidelines recommend screening for 9 disorders – Bloom syndrome, Canavan disease, cystic fibrosis, familial dysautonomia, Fanconi anemia group C, Gaucher disease type 1, mucolipidosis type IV, Niemann-Pick disease type A, and Tay-Sachs disease 

Epidemiology

Inheritance

  • Autosomal recessive

Pathophysiology

Clinical Presentation

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Ashkenazi Jewish Diseases, 16 Genes 0051415
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than those tested on this panel will not be detected

Diagnostic errors can occur due to rare sequence variations

Follow-up 

Cystic fibrosis (CF) carrier testing is not included in this panel

Order cystic fibrosis (CFTR) 165 pathogenic variants test to assess CF carrier status

Cystic Fibrosis (CFTR) 165 Pathogenic Variants 2013661
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Diagnostic errors can occur due to rare sequence variations

Only the 165 CFTR variants listed will be interrogated

The mild 5T variant, c.1210−12[5], will be reported only when R117H is detected and in individuals who are reported to be symptomatic

 

Hexosaminidase A Percent and Total Hexosaminidase, Plasma or Serum 2008121
Method: Quantitative Fluorometry

Limitations 

Pregnant women or women using oral contraceptives cannot be tested using plasma or serum because of high rates of false positives

In serum specimens, false positives can also be caused by several other conditions, including severe liver disease and autoimmune diseases

Testing in leukocytes should be used in these cases

Follow-up 

If plasma/serum results are inconclusive, perform leukocyte testing

Hexosaminidase A Percent and Total Hexosaminidase in Leukocytes 2008125
Method: Quantitative Fluorometry

Tay-Sachs Disease (HEXA), 7 Variants 0051428
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

HEXA variants other than those tested will not be detected

Diagnostic errors can occur due to rare sequence variations

Tay-Sachs Disease (HEXA) Sequencing and 7.6kb Deletion 2009298
Method: Polymerase Chain Reaction/Sequencing/Gel Electrophoresis

Limitations 

Regulatory region and deep intronic variants will not be detected

Large deletions/ duplications in HEXA, other than the 7.6 kb deletion, will not be detected

Diagnostic errors can occur due to rare sequence variations

Bloom Syndrome (BLM), 1 Variant 0051433
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than those tested will not be detected

Diagnostic errors can occur due to rare sequence variations

Canavan Disease (ASPA), 4 Variants 0051453
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than those tested will not be detected

Diagnostic errors can occur due to rare sequence variations

Fanconi Anemia, Group C (FANCC), 2 Variants 0051468
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than those tested will not be detected

Diagnostic errors can occur due to rare sequence variations

Dysautonomia, Familial (IKBKAP), 2 Variants 0051463
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than those tested will not be detected

Diagnostic errors can occur due to rare sequence variations

Gaucher Disease (GBA), 8 Variants 0051438
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than those tested will not be detected

Diagnostic errors can occur due to rare sequence variations

Mucolipidosis Type IV (MCOLN1), 2 Variants 0051448
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than those tested will not be detected

Diagnostic errors can occur due to rare sequence variations

Niemann-Pick Type A (SMPD1), 4 Variants 0051458
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than those tested will not be detected

Diagnostic errors can occur due rare sequence variations

ABCC8-Related Hyperinsulinism, 3 Variants 2013725
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than those tested will not be detected

Diagnostic errors can occur due to rare sequence variations

Glycogen Storage Disease, Type 1A (G6PC), 9 Variants 2013740
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than those tested will not be detected

Diagnostic errors can occur due to rare sequence variations

Joubert Syndrome Type 2 (TMEM216), 1 Variant 2013909
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than those tested will not be detected

Diagnostic errors can occur due to rare sequence variations

Lipoamide Dehydrogenase Deficiency (DLD), 2 Variants 2013735
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than those tested will not be detected

Diagnostic errors can occur due to rare sequence variations

Maple Syrup Urine Disease, Type 1B (BCKDHB), 3 Variants 2013730
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 
  • Variants other than those tested will not be detected

  • Diagnostic errors can occur due to rare sequence variations

NEB-Related Nemaline Myopathy, 1 Variant 2013745
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than those tested will not be detected

Diagnostic errors can occur due to rare sequence variations

Usher Syndrome, Types 1F and 3 (PCDH15 and CLRN1), 2 Variants 2013750
Method: Polymerase Chain Reaction/Fluorescence Monitoring

Limitations 

Variants other than those tested will not be detected

Diagnostic errors can occur due to rare sequence variations

Guidelines

ACOG Committee on Genetics. ACOG Committee Opinion No. 442: Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent. Obstet Gynecol. 2009; 114(4): 950-3. PubMed

Gross SJ, Pletcher BA, Monaghan KG, Professional Practice and Guidelines Committee. Carrier screening in individuals of Ashkenazi Jewish descent. Genet Med. 2008; 10(1): 54-6. PubMed

General References

Anderson SL, Ekstein J, Donnelly MC, Keefe EM, Toto NR, LeVoci LA, Rubin BY. Nemaline myopathy in the Ashkenazi Jewish population is caused by a deletion in the nebulin gene Hum Genet. 2004; 115(3): 185-90. PubMed

Ben-Yosef T, Ness SL, Madeo AC, Bar-Lev A, Wolfman JH, Ahmed ZM, Desnick RJ, Willner JP, Avraham KB, Ostrer H, Oddoux C, Griffith AJ, Friedman TB. A mutation of PCDH15 among Ashkenazi Jews with the type 1 Usher syndrome N Engl J Med. 2003; 348(17): 1664-70. PubMed

Edelmann L, Wasserstein MP, Kornreich R, Sansaricq C, Snyderman SE, Diaz GA. 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): 863-8. PubMed

Edvardson S, Shaag A, Zenvirt S, Erlich Y, Hannon GJ, Shanske AL, Gomori JM, Ekstein J, Elpeleg O. Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation Am J Hum Genet. 2010; 86(1): 93-7. PubMed

Ekstein J, Rubin BY, Anderson SL, Weinstein DA, Bach G, Abeliovich D, Webb M, Risch N. Mutation frequencies for glycogen storage disease Ia in the Ashkenazi Jewish population Am J Med Genet A. 2004; 129A(2): 162-4. PubMed

Fields RR, Zhou G, Huang D, Davis JR, Möller C, Jacobson SG, Kimberling WJ, Sumegi J. Usher syndrome type III: revised genomic structure of the USH3 gene and identification of novel mutations Am J Hum Genet. 2002; 71(3): 607-17. PubMed

German J, Sanz MM, Ciocci S, Ye TZ, Ellis NA. Syndrome-causing mutations of the BLM gene in persons in the Bloom's Syndrome Registry Hum Mutat. 2007; 28(8): 743-53. PubMed

Glaser B, Blech I, Krakinovsky Y, Ekstein J, Gillis D, Mazor-Aronovitch K, Landau H, Abeliovich D. ABCC8 mutation allele frequency in the Ashkenazi Jewish population and risk of focal hyperinsulinemic hypoglycemia Genet Med. 2011; 13(10): 891-4. PubMed

Kaback M, Desnick R. Hexosaminidase A Deficiency. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews, University of Washington, 1993-2015. Seattle, WA [Last updated Aug 2011; Accessed: Nov 2015]

Matalon R, Michals-Matalon K. Canavan Disease. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews, University of Washington, 1993-2015. Seattle, WA [Last updated Aug 2011; Accessed: Nov 2015]

Pastores G, Hughes D. Gaucher Disease. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews, University of Washington, 1993-2015. Seattle, WA [Last updated Feb 2015; Accessed: Nov 2015]

Sanz M, German J. Bloom's Review. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews, University of Washington, 1993-2015. Seattle, WA [Last updated Mar 2006; Accessed: Nov 2015]

Schiffmann R, Grishchuk Y, Goldin E. Mucolipidosis IV. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews, University of Washington, 1993-2015. Seattle, WA [Last updated Jul 2015; Accessed: Nov 2015]

Shaag A, Saada A, Berger I, Mandel H, Joseph A, Feigenbaum A, Elpeleg ON. Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews Am J Med Genet. 1999; 82(2): 177-82. PubMed

Shohat M, Hubshman M. Familial Dysautonomia. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews,. Seattle, WA [Last updated Dec 2014; Accessed: Nov 2015]

Wasserstein M, Schuchman E. Acid Sphingomyelinase Deficiency. In: Pagon RA, Adam MP, Ardinger HH, et al, editors. GeneReviews, University of Washington, 1993-2015. Seattle, WA [Last updated Jun 2015; Accessed: Nov 2015]

Medical Reviewers

Last Update: August 2017