Screening for five mutations detects 97% of cystic fibrosis (CF) chromosomes and predicts a carrier frequency of 1:29 in the Jewish Ashkenazi population

• Published in: American journal of human genetics Vol. 51; no. 5; pp. 951 - 956
• Main Authors: ABELIOVICH, D, LAVON, I. P, LERER, I, COHEN, T, SPRINGER, C, AVITAL, A, CUTTING, G. R
• Format: Journal Article
• Language: English
• Published: Chicago, IL University of Chicago Press 01.11.1992
• Subjects: Base Sequence; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; carriers; cystic fibrosis; Cystic Fibrosis - genetics; Cystic Fibrosis Transmembrane Conductance Regulator; FIBROSIS; frequency; Gastroenterology. Liver. Pancreas. Abdomen; Gene Frequency - genetics; GENE MUTATIONS; Genetic Carrier Screening; Genetic Testing; Heterozygote; HUMAN POPULATIONS; Humans; Israel - epidemiology; Jews - genetics; Liver. Biliary tract. Portal circulation. Exocrine pancreas; man; Medical sciences; Membrane Proteins - genetics; Molecular Sequence Data; mutation; Mutation - genetics; MUTATIONS; Oligodeoxyribonucleotides; Other diseases. Semiology; PATHOLOGICAL CHANGES; Polymerase Chain Reaction; POPULATIONS 550400 > Genetics; SCREENING; Asia; Israel; Human; Heterozygozity; Mucoviscidosis; Respiratory disease; Religion; Digestive diseases; Frequency; Mutation; Jew; Genetic disease; Pancreatic disease
• ISSN: 0002-9297; 1537-6605

To determine the distribution and frequency of cystic fibrosis (CF) mutations in the Israeli population, we have screened 96 patients for 11 relatively common mutations. Five mutations--delta F508, G542X, W1282X, N1303K, and 3849 + 10kb C-->T--were found to account for 97% of the CF alleles in the Ashkenazi Jews. In contrast, of the 11 mutations tested, only delta F508 was detected in Jewish patients of Sephardic or Oriental origin, accounting for 43% of the CF alleles. Four mutations--delta F508, G542X, W1282X, and N1303K--accounted for 55% of the CF alleles in Arab patients. In a pilot screening study, a random sample of 424 Ashkenazi individuals was analyzed for three mutations--delta F508, W1282X, and G542X. Thirteen individuals were detected as heterozygotes (six for delta F508 and seven for W1282X), predicting a heterozygote frequency of 1:29. This is similar to the frequency of carriers in the Caucasian population of northern European ancestry. On the basis of these data, the Ashkenazi population is considered to be a candidate for CF heterozygote screening.