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Updated: May 13, 2026
Mutagenesis and Analysis of Genetic Mutations in the GC-rich KISS1 Receptor Sequence Identified in Humans with Reproductive Disorders
Published on: September 4, 2011
Identification of HESX1 mutations in Kallmann syndrome
Kayce Newbern1, Nithya Natrajan, Hyung-Goo Kim
1Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology, Infertility, and Genetics, Medical College of Georgia, Georgia Health Sciences University, Augusta, Georgia 30912, USA.
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.
