Identification of HESX1 mutations in Kallmann syndrome

Kayce Newbern, Nithya Natrajan, Hyung Goo Kim, Lynn P. Chorich, Lisa M. Halvorson, Richard S Cameron, Lawrence C Layman

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1831-1837
Number of pages7
JournalFertility and sterility
Volume99
Issue number7
DOIs
StatePublished - Jun 1 2013

Fingerprint

Kallmann Syndrome
Mutation
Missense Mutation
Phenotype
DNA
DNA Sequence Analysis
Genotype
Outcome Assessment (Health Care)
Polymerase Chain Reaction
Idiopathic Hypogonadotropic Hypogonadism
Genes

Keywords

  • GnRH deficiency
  • HESX1
  • Kallmann syndrome
  • delayed puberty
  • hypogonadotropic hypogonadism

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Identification of HESX1 mutations in Kallmann syndrome. / Newbern, Kayce; Natrajan, Nithya; Kim, Hyung Goo; Chorich, Lynn P.; Halvorson, Lisa M.; Cameron, Richard S; Layman, Lawrence C.

In: Fertility and sterility, Vol. 99, No. 7, 01.06.2013, p. 1831-1837.

Research output: Contribution to journalArticle

Newbern, K, Natrajan, N, Kim, HG, Chorich, LP, Halvorson, LM, Cameron, RS & Layman, LC 2013, 'Identification of HESX1 mutations in Kallmann syndrome', Fertility and sterility, vol. 99, no. 7, pp. 1831-1837. https://doi.org/10.1016/j.fertnstert.2013.01.149
Newbern K, Natrajan N, Kim HG, Chorich LP, Halvorson LM, Cameron RS et al. Identification of HESX1 mutations in Kallmann syndrome. Fertility and sterility. 2013 Jun 1;99(7):1831-1837. https://doi.org/10.1016/j.fertnstert.2013.01.149
Newbern, Kayce ; Natrajan, Nithya ; Kim, Hyung Goo ; Chorich, Lynn P. ; Halvorson, Lisa M. ; Cameron, Richard S ; Layman, Lawrence C. / Identification of HESX1 mutations in Kallmann syndrome. In: Fertility and sterility. 2013 ; Vol. 99, No. 7. pp. 1831-1837.
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