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Ashkenazi Jewish Panel

Ashkenazi Jewish Panel

Test Highlight

Ashkenazi Jewish Panel

  

Clinical Use

  • Determine carrier status in Ashkenazi Jewish individuals

  • Assess risk of having a child with any of 11 disorders commonly found in the Ashkenazi Jewish population (11-test panel) or any of the 4 disorders for which testing is recommended by the American Congress of Obstetricians and Gynecologists (ACOG) and the American College of Medical Genetics (ACMG) (4-test panel)

Clinical Background

The Ashkenazi Jewish panels detect mutations associated with disorders that commonly occur in Ashkenazi Jewish (Eastern European Jewish) individuals (see below). Two panels are offered: 1) a 4-test panel, which includes the genetic tests recommended by ACOG and ACMG (for Canavan disease, cystic fibrosis, familial dysautonomia, and Tay-Sachs); and 2) an 11-test panel, which also includes tests for 7 other diseases common among Ashkenazi Jewish individuals. The panels simplify test ordering for Ashkenazi Jewish individuals who wish to know their carrier status and/or their risk of having a child with any of these disorders. It is most frequently used for Ashkenazi Jews and their partners who are pregnant or contemplating pregnancy. Since all of these disorders are autosomal recessive, both parents must be carriers for the couple to have an affected child. If one partner is Ashkenazi Jewish and the other is not, sequential screening, beginning with the Ashkenazi Jewish individual, is recommended.

A brief description of each disorder follows.

Bloom Syndrome

Children with Bloom syndrome are affected with growth retardation, abnormalities in skin pigmentation, immunodeficiency, a predisposition to cancer, and chromosomal instability. Death usually results from cancer at a mean age of 27.

Canavan Disease

Canavan disease (aspartoacylase deficiency) is a progressive neurologic disease characterized by increased head circumference, decreasing muscle tone and motor activity, progressive loss of visual responsiveness, and mental retardation. Death usually occurs in the first few years of life, although some individuals survive into their teens.

Cystic Fibrosis

Characteristic manifestations include recurrent lung infections, malabsorption, malnutrition, and infertility (especially in males). Median survival is approximately 37 years.

Familial Dysautonomia

Familial dysautonomia is characterized by abnormal functioning of the sensory and autonomic nervous systems. This causes decreased sensitivity to pain, abnormal regulation of body temperature, paroxysmal hypertension, and gastrointestinal abnormalities.

Fanconi Anemia Group C

Fanconi anemia is characterized by deficient bone development and bone marrow function. This can lead to pancytopenia, anemia, leukemia, and malformations of the limbs, kidneys, and heart. The disorder may be mild or severe.

Gaucher Disease

Gaucher disease is a lysosomal glycolipid storage disorder caused by an enzymatic deficiency (acid beta- galactosidase deficiency). Individuals may have an enlarged liver and spleen, thrombocytopenia, anemia, bone pain, bone lesions, and fractures. Life expectancy depends on severity of the symptoms.

Glycogen Storage Disease Type 1a

This disorder is caused by a toxic buildup of glycogen and fat in the liver, kidneys, and small intestines. Affected children tend to have short stature, thin arms and legs, and enlarged liver and kidneys. Adults may have osteoporosis, gout, kidney disease, pulmonary hypertension, and polycystic ovary disease.

Maple Syrup Urine Disease

This disease is caused by buildup of leucine, isoleucine, and valine. Affected infants show poor feeding, vomiting, lethargy, delayed development, and sweet-smelling urine. Untreated disease can lead to seizures, coma, and death within the first few months after birth.

Mucolipidosis IV

This neurodegenerative lysosomal storage disorder is characterized by growth and psychomotor retardation, progressive retinal degeneration, clouding of the cornea, and crossed eyes. The majority of infants with the disorder fail to develop past the level of a 1- to 2-year-old and never speak or walk. They may have a normal life expectancy.

Niemann-Pick Disease Types A and B

This lysosomal storage disorder is characterized by diminished acid sphingomyelinase activity. Type A is usually fatal within 3 to 5 years. These children fail to thrive, have an enlarged liver and spleen, and exhibit progressive mental and physical degeneration. Individuals with type B also have hepatosplenomegaly (along with cirrhosis, portal hypertension, ascites, and pancytopenia), but little to no neurologic involvement. They often survive into adolescence and adulthood.

Tay-Sachs Disease

Tay-Sachs disease is a progressive, neurodegenerative disorder caused by an enzymatic deficiency (hexosaminidase A). The classic infantile form is characterized by developmental retardation followed by paralysis, dementia, seizures, and blindness. Death usually occurs by age 4.

Method

All tests, with the exception of the CF screen, are carried out by multiplex-polymerase chain reaction (PCR) amplification, allele-specific primer extension, and allelic discrimination using color-coded microspheres. The CF screen is carried out by PCR amplification with allelic discrimination using an oligonucleotide ligation-based assay. Table 1 shows the names and codes of individual tests in the 11-test panel. Information in the first 4 rows also applies to the 4-test panel. The number of mutations detected, the carrier detection rate, and the residual risk for each disorder in the Ashkenazi Jewish population are listed in Table 2.

Table 1. Individual Tests Included in the Panels
Test Code Test Name
90905a Canavan Disease Mutation Analysis
10458b Cystic Fibrosis Screen
90912a Familial Dysautonomia Mutation Analysis
90903a Tay-Sachs Disease Mutation Analysis
90872a Bloom Syndrome DNA Mutation Analysis
90897a Fanconi Anemia DNA Mutation Analysis
90907a Gaucher Disease, DNA Mutation Analysis
90915a Glycogen Storage Disease Type 1a Mutation Analysis
90909a Maple Syrup Disease (MSUD) Mutation Analysis
90899a Mucolipidosis Type IV Mutation Analysis
90893a Niemann-Pick Disease Mutation Analysis

a This test was developed and its performance characteristics have been determined by Quest Diagnostics Nichols Institute. Performance characteristics refer to the analytical performance of the test.
b The performance characteristics of this assay have been determined by Quest Diagnostics Nichols Institute. Performance characteristics refer to the analytical performance of the test.

Table 2. Carrier Frequency, Detection Rate, and Residual Risk of Carrying a Mutation in the Ashkenazi Jewish Population
Disease Carrier
Frequency

Number of

Mutations
Detected

Carrier Detection Rate (%)

Residual
Risk
Bloom syndrome 1 in 100 1 97 1:3300
Canavan disease 1 in 40 4 99 1:3900
Cystic fibrosis 1 in 24 32a 94 1:400
Familial dysautonomia 1 in 30 2 99.5 1:5800
Fanconi anemia group C 1 in 89 2 99 1:8800
Gaucher disease 1 in 13 8 96 1:301
Glycogen storage disease type 1a 1:71 2 >99 1:7000
Maple syrup urine disease 1:113 3 >99 1:11,000
Mucolipidosis type IV 1 in 100 2 95 1:2000
Niemann-Pick disease 1 in 90 (type A)
Unknown (type B)
4 95

1:1780
Tay-Sachs disease 1 in 30 7b 98 1:1450

a Includes the 23 mutations recommended by the American College of Medical Genetics (ACMG) and the American Congress of Obstetricians and Gynecologists (ACOG), as well as 9 other mutations.
b Five Tay-Sachs disease mutations and 2 pseudodeficiency alleles. The pseudodeficiency alleles are not associated with disease but can cause false-positive enzyme assay results.

Interpretive Information

The presence of a single mutation in an asymptomatic individual identifies that person as a carrier. The absence of a mutation(s) significantly reduces, but does not eliminate, the risk of being a carrier. The residual risk of being a carrier (ie, of having a mutation not screened for in this assay) is influenced by the individual’s clinical and family history and ethnicity. Table 2 lists the residual risk of being a carrier for each disorder following a negative test result in an individual of full Ashkenazi-Jewish heritage.

Since genetic variation and other problems can affect the accuracy of direct mutation testing, the results for all 11 tests should always be interpreted in light of clinical and familial data. DNA-based testing is highly accurate, but rare false negative/false positive results may occur.

Additional assistance in interpretation of results is available from our Genetic Counselors by calling 866-GENE-INFO (866-436-3463).

References

  1. American College of Medical Genetics. Technical standards and guidelines for CFTR mutation testing. 2006 ed. http://www.acmg.net/Pages/ACMG_Activities/stds-2002/cf.htm#Table1. Accessed March 26, 2013.

  2. Committee on Genetics, American College of Obstetricians and Gynecologists. ACOG Committee Opinion. Number 486, April 2011. Update on carrier screening for cystic fibrosis. Obstet Gynecol. 2011;117:1028-1031.

  3. Committee on Genetics, American College of Obstetricians and Gynecologists. ACOG Committee Opinion. Number 442, October 2009. Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent. Obstet Gynecol. 2009;114:950-953.

  4. Genetics Home Reference. Glycogen storage disease type 1. http://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-i. Updated September 2010. Accessed March 26, 2013.

  5. Genetics Home Reference. Maple syrup urine disease. http://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease. Updated December 2008. Accessed March 26, 2013.

  6. Monaghan KG, Feldman GL, Palomaki GE, et al; the Ashkenazi Jewish Reproductive Screening Working Group and the Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee. Genet Med. 2008;10:57-72.

 

Content reviewed 06/2013

 
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* The tests listed by specialist are a select group of tests offered. For a complete list of Quest Diagnostics tests, please refer to our Directory of Services.