HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Antelli, A. Articles by Cicognani, A. Search for Related Content PubMed PubMed Citation Articles by Antelli, A. Articles by Cicognani, A.

Two novel GnRHR gene mutations in two siblings with hypogonadotropic hypogonadism

Department of Paediatrics and Centro Inter Ateneo di Ricerca di Genomica in Endocrinologia Pediatrica (CIGEP), University of Bologna, 40138 Bologna, Italy and ¹ S. Orsola-Malpighi Hospital, 40138 Bologna, Italy

(Correspondence should be addressed to A Cicognani; Email: cicogna{at}alma.unibo.it)

Abstract

Objective: Mutations in the gonadotropin-releasing hormone receptor (GnRHR) gene are the cause of isolated hypogonadotropic hypogonadism (HH). We describe the molecular investigations of the GnRHR gene in two siblings affected by HH and their clinical course.

Design: The female was referred at age 14 for pubertal delay with no secondary sexual signs, whereas the male had been followed since prepuberty. Hormonal evaluation showed very low levels of gonadotropins, luteinizing hormone-releasing hormone test (LHRH test) and sexual steroids in both patients, suggesting a possible defect in the mechanism of action of the GnRH gene on its receptor.

Methods: The GnRHR gene of the two siblings and their parents were analyzed by PCR followed by direct sequencing.

Results: Two new single nucleotide substitutions resulting in the T104I and the Y108C substitutions in the first extracellular loop (ECL1) were identified in both siblings. The molecular analysis confirmed the carrier status of the parents.

Conclusions: We identified two new missense mutations in the GnRHR gene in two siblings with HH. The nature of the substitutions lying in the ECL1 involved in the ligand–receptor interaction, as well as the high conservation of the two residues in all mammalian GnRHR, are suggestive of some implications in the phenotype observed.

This article has been cited by other articles:

				A. A. Sinisi, R. Asci, G. Bellastella, L. Maione, D. Esposito, A. Elefante, A. De Bellis, A. Bellastella, and A. Iolascon Homozygous mutation in the prokineticin-receptor2 gene (Val274Asp) presenting as reversible Kallmann syndrome and persistent oligozoospermia: Case Report Hum. Reprod., July 1, 2008; (2008) den247v1. [Abstract] [Full Text] [PDF]