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Molecular analysis of the neuropeptide Y1 receptor gene in human idiopathic gonadotropin-dependent precocious puberty and isolated hypogonadotropic hypogonadism.

Abstract：

OBJECTIVE:To investigate the role of mutations or polymorphisms in the NPY-Y1R gene in human idiopathic central pubertal disorders. DESIGN:Molecular studies. SETTING:University hospital. PATIENT(S):Thirty-three patients with gonadotropin-dependent precocious puberty, 22 with hypogonadotropic hypogonadism, and 50 controls. INTERVENTION(S):Genomic DNA extraction, NPY-Y1R gene sequence analysis, cell-surface expression, and functional activity of an identified receptor variant. MAIN OUTCOME MEASURE(S):Results of sequencing, cell-surface receptor expression, and receptor function. RESULT(S):A heterozygous substitution of lysine (K) by threonine (T) at position 374 in the carboxyl terminal region of NPY-Y1R was identified in a girl with familial GDPP. Her mother, who had pubertal developmental at appropriate age, carried the same genetic variant. Introduction of the K374T variant into an expression vector containing the human NPY-Y1R complementary DNA led to a partial reduction in cell-surface expression of NPY-Y1R in transiently transfected HEK293 cells. This mutation did not lead to a significant reduction in NPY-stimulated activity of the receptor in this heterologous expression system. No other allelic variants of the NPY-Y1R gene were identified in patients or controls. CONCLUSION(S):We have identified an inherited heterozygous variant of the NPY-Y1R gene in a girl with precocious puberty; however, this most likely did not contribute to her phenotype. Mutations of the highly conserved NPY-Y1R gene do not appear to represent a frequent mechanism underlying human idiopathic central pubertal disorders.

journal_name

Fertil Steril

journal_title

Fertility and sterility

authors

Freitas KC,Ryan G,Brito VN,Tao YX,Costa EM,Mendonca BB,Segaloff D,Latronico AC

doi

10.1016/j.fertnstert.2006.07.1519

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

627-34

issue

3

eissn

0015-0282

issn

1556-5653

pii

S0015-0282(06)04043-X

journal_volume

87

pub_type

杂志文章

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