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Fertil Steril. 2013 Jun;99(7):1831-7. doi: 10.1016/j.fertnstert.2013.01.149. Epub 2013 Mar 1.

Identification of HESX1 mutations in Kallmann syndrome.

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  • 1Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology, Infertility, and Genetics, Medical College of Georgia, Georgia Health Sciences University, Augusta, Georgia 30912, USA.

Abstract

OBJECTIVE:

To determine whether HESX1 mutations are present in patients with idiopathic hypogonadotropic hypogonadism (IHH)/Kallmann syndrome (KS).

DESIGN:

Polymerase chain reaction-based DNA sequencing was performed on 217 well-characterized IHH/KS patients. Putative missense mutations were analyzed by sorting intolerant from tolerant (SIFT) and Clustal Ω.

SETTING:

Academic medical center.

PATIENT(S):

Two hundred seventeen patients with IHH/KS and 192 controls.

INTERVENTION(S):

Deoxyribonucleic acid was extracted from patients and controls; genotype/phenotype comparisons were made.

MAIN OUTCOME MEASURE(S):

Deoxyribonucleic acid sequence of HESX1, SIFT analysis, and ortholog alignment.

RESULT(S):

Two novel heterozygous missense mutations (p.H42Y and p.V75L) and previously reported heterozygous missense mutation p.Q6H in HESX1 were identified in 3 of 217 patients (1.4%). All were males with KS. Both p.Q6H and p.H42Y were predicted to be deleterious by SIFT, whereas p.V75L was conserved in 8 of 9 species. No other IHH/KS gene mutations were present.

CONCLUSION(S):

HESX1 mutations may cause KS in addition to more severe phenotypes. Our findings expand the phenotypic spectrum of HESX1 mutations in humans, thereby broadening its role in development.

Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

PMID:
23465708
[PubMed - indexed for MEDLINE]
PMCID:
PMC3888813
Free PMC Article
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