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 N1303K A455E R347P 3849+10kbC->T

deltaI507 R553X R560T 711+1G->T 2789+5G->A

G542X 621+1G->T R1162X 1898+1G->A 3659delC

G551D R117H G85E 2184delA I148T

W1282X 1717-1G->A R334W 1078delT 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	511de l6434				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.