Genetic heterogeneity evidenced by low incidence of KAL-1 gene mutations in sporadic cases of gonadotropin-releasing hormone deficiency

Details

Serval ID
serval:BIB_887B2641B77F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genetic heterogeneity evidenced by low incidence of KAL-1 gene mutations in sporadic cases of gonadotropin-releasing hormone deficiency
Journal
Journal of Clinical Endocrinology and Metabolism
Author(s)
Georgopoulos  N. A., Pralong  F. P., Seidman  C. E., Seidman  J. G., Crowley, W. F., Jr. , Vallejo  M.
ISSN
0021-972X (Print)
Publication state
Published
Issued date
01/1997
Volume
82
Number
1
Pages
213-7
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jan
Abstract
Isolated GnRH deficiency is a heritable condition characterized by a functional deficit in GnRH secretion. Familial cases with different modes of inheritance have been described, and the gene responsible for the X-linked form (KAL-1) has been identified. However, sporadic cases with no documented family history of GnRH deficiency account for the majority of the affected patients. For this reason, we sought to determine the frequency with which KAL-1 gene mutations occur in patients with sporadic GnRH deficiency. Only 1 of 21 patients with sporadic GnRH deficiency was found to bear a defect in the KAL-1 gene (a deletion of 14 bases starting at codon 464). Three types of polymorphic single base substitutions with no apparent correlation with GnRH deficiency were also detected in several patients. In each of 3 different patients with an X-linked mode of inheritance, 3 genetic defects, 2 point mutations and a small intragenic deletion, were detected. These defects consist of a single base mutation introducing a stop codon at position 328, a single base mutation resulting in a phenylalanine to leucine substitution at position 517, and a 9-base deletion at the 3'-exon-intron splice site of exon 8, respectively. All identified genetic defects occur within the fibronectin type III repeats of the predicted protein encoded by the KAL-1 gene. In conclusion, our study indicates that the incidence of genetic defects within the coding region of the KAL-1 gene in patients with sporadic GnRH deficiency is low (5-8%), thus supporting the idea that the X-linked form of inheritance represents the least common form of the disease.
Keywords
Base Sequence Gene Deletion *Genetic Heterogeneity Gonadotropin-Releasing Hormone/*deficiency/*genetics Humans Kallmann Syndrome/*genetics Linkage (Genetics) Male *Mutation Pedigree Point Mutation Polymorphism, Genetic Repetitive Sequences, Nucleic Acid X Chromosome
Pubmed
Web of science
Create date
25/01/2008 17:26
Last modification date
20/08/2019 15:47
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