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PMID: 7539210 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

CFTR haplotype analysis reveals genetic heterogeneity in the etiology of congenital bilateral aplasia of the vas deferens.

American journal of human genetics ·Vol. 56 ·No. 6 ·1995-06-00 ·Pages 1359-66

Rave-Harel N, Madgar I, Goshen R, Nissim-Rafinia M, Ziadni A, Rahat A, Chiba O, Kalman YM, Brautbar C, Levinson D

Abstract

Congenital bilateral aplasia of the vas deferens (CBAVD) was suggested to be a mild form of cystic fibrosis (CF). Mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in males with CBAVD revealed that in some males CBAVD is caused by two defective CFTR alleles. The genetic basis of CBAVD in the other males and its association with CF remained unclear. We undertook this study to test the hypothesis of commonality of CBAVD and CF by haplotype analysis, in the CFTR locus, of males suffering from CBAVD and of their families. According to the hypothesis of commonality of CBAVD and CF, two brothers with CBAVD are expected to carry the same two CFTR alleles, while their fertile brothers are expected to carry at least one different allele. Eleven families were studied, of which two families, with unidentified CFTR mutations, did not support this hypothesis. In these families two brothers with CBAVD inherited different CFTR alleles. Their fertile brothers inherited the same CFTR alleles as their brothers with CBAVD. These results provide evidence for genetic heterogeneity in CBAVD. Though in some families CBAVD is associated with two CFTR mutations, we suggest that in others it is caused by other mechanisms, such as mutations at other loci or homozygosity or heterozygosity for partially penetrant CFTR mutations.

MeSH Terms
Congenital Abnormalities/epidemiology,etiology Cystic Fibrosis/genetics Cystic Fibrosis Transmembrane Conductance Regulator Female Genetic Heterogeneity Haplotypes Humans Infertility, Male/genetics Israel/epidemiology Male Membrane Proteins/genetics Models, Genetic Sequence Analysis, DNA Vas Deferens/abnormalities
Chemicals
CFTR protein, human Membrane Proteins Cystic Fibrosis Transmembrane Conductance Regulator
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Rave-Harel N
Department of Genetics, Life Sciences Institute, Hebrew University of Jerusalem, Israel.
Madgar I
Goshen R
Nissim-Rafinia M
Ziadni A
Rahat A
Chiba O
Kalman Y M
Brautbar C
Levinson D
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
Published
1995-06-00
Pages
1359-66
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1801105
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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