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Title: Exclusion of growth hormone (GH)-releasing hormone gene mutations in familial isolated GH deficiency by linkage and single strand conformation analysis

Abstract

The molecular basis and the locus responsible for most familial cases of isolated GH deficiency (IGHD) are still unknown. The GH-releasing hormone (GHRH) gene has been evaluated as a possible candidate in 23 unrelated families with IGHD, 14 of whom were classified as having autosomal recessive IGHD type IB and 9 of whom had autosomal dominant IGHD type II. Three highly polymorphic microsatellites (dinucleotide repeats), mapped close to GHRH on chromosome 20 by previous linkage studies, were analyzed as markers for the GHRH locus. All available family members were genotyped for D20S44 [no recombination with GHRH at a LOD (logarithm of the odds) score of 3.6]. Noninformative families were also genotyped for D20S45 and/or D20S54 (located at {approximately} 1 and 3 centiMorgan of genetic distance from GHRH, respectively). Twenty families were informative for linkage analysis with 1 or more of these markers. They found at least 1 obligate recombinant with discordance between phenotype and genotype in 19 of the 23 families (83%). There is only a very small chance (1-3% or less) that the discordances observed are due to recombination between the GHRH locus and the marker tested. Concordant segregation was seen in only 1 type IB family (4%). Whenmore » probands from this and the 3 noninformative families were screened for sequence variants in the 5 exons of the GHRH gene by single strand conformation analysis, no abnormal patterns were observed. They conclude that mutations responsible for IGHD are not within or near the structural gene for GHRH on chromosome 20 in the 23 families studied. As linkage to the GH-1 gene has also been previously excluded in 65% of these families, mutations in a locus or loci unlinked to GH-1 and GHRH must be responsible for the majority of these IGHD families. 31 refs., 4 figs., 1 tab.« less

Authors:
;  [1];  [2]
  1. Stanford Univ. School of Medicine, CA (United States)
  2. Vanderbilt Univ. School of Medicine, Nashville, TN (United States)
Publication Date:
OSTI Identifier:
39422
Resource Type:
Journal Article
Journal Name:
Journal of Clinical Endocrinology and Metabolism
Additional Journal Information:
Journal Volume: 78; Journal Issue: 3; Other Information: PBD: Mar 1994
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; STH; METABOLIC DISEASES; LIBERINS; GENE MUTATIONS; GENETIC MAPPING; HUMAN CHROMOSOMES

Citation Formats

Perez Jurado, L.A., Francke, U., and Phillips, J.A. III. Exclusion of growth hormone (GH)-releasing hormone gene mutations in familial isolated GH deficiency by linkage and single strand conformation analysis. United States: N. p., 1994. Web. doi:10.1210/jc.78.3.622.
Perez Jurado, L.A., Francke, U., & Phillips, J.A. III. Exclusion of growth hormone (GH)-releasing hormone gene mutations in familial isolated GH deficiency by linkage and single strand conformation analysis. United States. doi:10.1210/jc.78.3.622.
Perez Jurado, L.A., Francke, U., and Phillips, J.A. III. Tue . "Exclusion of growth hormone (GH)-releasing hormone gene mutations in familial isolated GH deficiency by linkage and single strand conformation analysis". United States. doi:10.1210/jc.78.3.622.
@article{osti_39422,
title = {Exclusion of growth hormone (GH)-releasing hormone gene mutations in familial isolated GH deficiency by linkage and single strand conformation analysis},
author = {Perez Jurado, L.A. and Francke, U. and Phillips, J.A. III},
abstractNote = {The molecular basis and the locus responsible for most familial cases of isolated GH deficiency (IGHD) are still unknown. The GH-releasing hormone (GHRH) gene has been evaluated as a possible candidate in 23 unrelated families with IGHD, 14 of whom were classified as having autosomal recessive IGHD type IB and 9 of whom had autosomal dominant IGHD type II. Three highly polymorphic microsatellites (dinucleotide repeats), mapped close to GHRH on chromosome 20 by previous linkage studies, were analyzed as markers for the GHRH locus. All available family members were genotyped for D20S44 [no recombination with GHRH at a LOD (logarithm of the odds) score of 3.6]. Noninformative families were also genotyped for D20S45 and/or D20S54 (located at {approximately} 1 and 3 centiMorgan of genetic distance from GHRH, respectively). Twenty families were informative for linkage analysis with 1 or more of these markers. They found at least 1 obligate recombinant with discordance between phenotype and genotype in 19 of the 23 families (83%). There is only a very small chance (1-3% or less) that the discordances observed are due to recombination between the GHRH locus and the marker tested. Concordant segregation was seen in only 1 type IB family (4%). When probands from this and the 3 noninformative families were screened for sequence variants in the 5 exons of the GHRH gene by single strand conformation analysis, no abnormal patterns were observed. They conclude that mutations responsible for IGHD are not within or near the structural gene for GHRH on chromosome 20 in the 23 families studied. As linkage to the GH-1 gene has also been previously excluded in 65% of these families, mutations in a locus or loci unlinked to GH-1 and GHRH must be responsible for the majority of these IGHD families. 31 refs., 4 figs., 1 tab.},
doi = {10.1210/jc.78.3.622},
journal = {Journal of Clinical Endocrinology and Metabolism},
number = 3,
volume = 78,
place = {United States},
year = {1994},
month = {3}
}