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 language | English |
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Pages (from-to) | 1831-1837 |
Number of pages | 7 |
Journal | Fertility and Sterility |
Volume | 99 |
Issue number | 7 |
DOIs | |
Publication status | Published - Jun 2013 |
Externally published | Yes |
Keywords
- GnRH deficiency
- HESX1
- Kallmann syndrome
- delayed puberty
- hypogonadotropic hypogonadism