MUTATION IN THE FOLLICLE-STIMULATING-HORMONE RECEPTOR GENE CAUSES HEREDITARY HYPERGONADOTROPIC OVARIAN FAILURE

被引:733
作者
AITTOMAKI, K
LUCENA, JLD
PAKARINEN, P
SISTONEN, P
TAPANAINEN, J
GROMOLL, J
KASKIKARI, R
SANKILA, EM
LEHVASLAIHO, H
ENGEL, AR
NIESCHLAG, E
HUHTANIEMI, I
DELACHAPELLE, A
机构
[1] UNIV TURKU,DEPT PHYSIOL,SF-20520 TURKU,FINLAND
[2] FINNISH RED CROSS & BLOOD TRANSFUS SERV,SF-00310 HELSINKI,FINLAND
[3] UNIV OULU,CENT HOSP,DEPT OBSTET & GYNECOL,SF-90220 OULU,FINLAND
[4] UNIV MUNSTER,INST REPROD MED,D-48149 MUNSTER,GERMANY
[5] UNIV MALAGA,FAC MED,DEPT BIOCHEM & MOLEC BIOL,E-29080 MALAGA,SPAIN
[6] UNIV HELSINKI,CENT HOSP,DEPT CLIN GENET,SF-00290 HELSINKI,FINLAND
[7] UNIV HELSINKI,CENT HOSP,DEPT OBSTET & GYNECOL,SF-00290 HELSINKI,FINLAND
基金
芬兰科学院;
关键词
D O I
10.1016/0092-8674(95)90275-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hypergonadotropic ovarian dysgenesis (ODG) with normal karyotype is a heterogeneous condition that in some cases displays Mendelian recessive inheritance, By systematically searching for linkage in multiplex affected families, we mapped a locus for ODG to chromosome 2p, As the previously cloned follicle-stimulating hormone receptor (FSHR) gene had been assigned to 2p, we searched it for mutations, A C566T transition in exon 7 of FSHR predicting an Ala to Val substitution at residue 189 in the extracellular ligand-binding domain segregated perfectly with the disease phenotype. Expression of the gene in transfected cells demonstrated a dramatic reduction of binding capacity and signal transduction, but apparently normal ligand-binding affinity of the mutated receptor. We conclude that the mutation causes ODG in these families.
引用
收藏
页码:959 / 968
页数:10
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