General Medical Information

Inactivating Luteinizing Hormone Receptor Mutations

Joe Leigh Simpson

Another trophic hormone receptor gene in which a mutation causes gonadal dysgenesis is the LHR. Most LHR mutations have occurred in 46,XY cases, but 46,XX cases occurred in sibships in which an affected 46,XY male had Leydig cell hypoplasia.

Latronico reported primary amenorrhea in a 22-year-old woman. In that family, three males and one female had a homozygous nonsense (stop) mutation at codon 554 (C554X). The resulting stop codon produced a truncated protein having five rather than seven transmembrane domains. The affected female had breast development but only a single episode of menstrual bleeding at age 20 years; LH was 37 mIU/mL and FSH was 9 mIU/mL. The mutation reduced signal transduction activity of the LHR gene. In another 46,XX case reported by Toledo, secondary amenorrhea occurred; LH and FSH were 10 and 9 mIU/mL, respectively; the mutation was Ala 593Pro.

Activating LHR mutations seems to have little effect in females, although in males precocious puberty occurs.