Tests and Indications

Cystic Fibrosis

Cystic fibrosis is the most common genetic disorder among Caucasians (1:29) and is less common among other ethnic groups (see table below).

The American College of Medical Genetics (ACMG) recommends that CF screening be offered to couples considering starting a family and recommends the mutation panel listed below for all ethnicities.

The detection rate differs with ethnic origin and is shown along with after testing residual risk estimates in the table below.

Mutations Analyzed

deltaF508	deltaI507	G542X	G551D	W1282X
N1303K	R553X	621+1G->T	R117H	1717-1G->A
A455E	R560T	R1162X	G85E	R334W
R347P	711+1G->T	1898+1G->A	2184delA	1078delT
3849+10kbC->T	2789+5G->A	3659delC	I148T	3120+1G->A

This test distinguishes the F508C, I507V, and I506V polymorphisms and the poly T allele is reported where clinically significant.

Sensitivity and Estimated Carrier Risk

		Estimated Carrier Risk
Ethnic Group	Detection Rate	Before Test	After Test
Ashkenazi Jewish	97%	1/29	~1 in 930
European Caucasian	80%	1/29	~1 in 140
African American	69%	1/65	~1 in 207
Hispanic American	57%	1/46	~1 in 105
Asian American	ND	1/90	ND

Ashkenazi Jewish Genetic Disease Screening

A video entitled: "The Importance of Genetic Screening for Ashkenazi Jewish People" is available on our website and may be shared with your patients.

See the video: Genetic Screening Video (real player needed)

The Molecular Genetics Laboratory currently provides direct mutation detection for ten inherited diseases common in the Ashkenazi Jewish population.

The diseases and the mutations screened are listed in the table below.

These tests may be used for both carrier screening and diagnosis of symptomatic individuals.

For couples of mixed ethnicity it is recommended that the Jewish partner be tested first. Contact the laboratory to determine appropriate testing procedures for individuals of mixed heritage.

Disease	Mutations Detected	Sensitivity in Ashkenazi Jews
Bloom Syndrome	blm-ASH (6 bp deletion and 7 bp insertion at nucleotide 2281 of the BLM gene)	99%
Canavan Disease	Y231X E285A	98%
Gaucher Disease	R496H N370S 84GG IVS2+1 L444P	99%
Glycogen Storage Disease,1A	R83C	98%
Fanconi Anemia, Type C*	IVS4+ 4A>T	98%
Familial Dysautonomia	2507+6T>C	99%
Familial Hyperinsulinism	IVS32-9>A delta F1388	88%
Maple Syrup Urine Disease	R183P	90%
Mucolipidosis, Type 4	IVS3-2A>3 511del6434	94%
Tay-Sachs Disease	1277insTATC 1421+1G>C G269S	98%

* Fanconi Anemia is a complex disease caused by at least 11 different genes.

Among Ashkenazi Jews, a single founder mutation in the FANCC gene is responsible for 98% of cases of Fanconi Anemia in this population.

For non-Jewish individuals, chromosomal breakage studies should be considered. This type of testing is available in the laboratory of Dr. Arleen Auerbach at Rockefeller University.