PLEKHA6 — nouveau gène associé à l'hypogonadisme hypogonadotrope idiopathique (IHH)
Variant / mechanism
PLEKHA6 (18 missense variants: PH, proline-rich, coiled-coil, C-term domains)
New IHH gene (~1.3% of cases) — novel mechanism via impaired kisspeptin secretion
Summary
Systematic ES/WGS analysis of a cohort of 1,822 IHH patients: 18 distinct PLEKHA6 variants identified in 24 patients from 20 independent families. Missense variants distribute across PH, proline-rich, coiled-coil, and C-term domains. Estimated frequency ~1.3%, comparable to major known IHH genes. Identified mechanism: impaired kisspeptin secretion, not previously implicated in reproductive deficiency.
Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.
Analysis
Major discovery in reproductive genetics: a new IHH gene with an original molecular mechanism (kisspeptin). To be added to IHH/Kallmann panels without delay. Consider kisspeptin assays in translational research.
Why this score?
new gene +3; new mechanism (kisspeptin) +2; functional analysis +2; 1822-patient cohort +1; clinical impact +1; preprint but robust methodology +1