The follicle-stimulating hormone receptor gene is polymorphic in premature ovarian failure and normal controls

Objective: To examine the FSH receptor gene for detectable abnormalities in women with premature ovarian failure. Design: Study of genomic DNA from controls and from patients with 46,XX premature ovarian failure (POF). Setting: Clinics and laboratories of university gynecology and obstetrics departments. Patients: Twenty-one women with 46,XX POF and 40 normal fertile controls. Interventions: Deoxyribonucleic acid was analyzed in patients and controls by Southern blot analysis, polymerase chain reaction (PCR), and denaturing gradient gel electrophoresis. Southern blots were hybridized with the FSH receptor complementary DNA and other smaller DNA probes. Exons 1, 5 to 6, and 10 were amplified by PCR and electrophoresed on agarose gels. Polymerase chain reaction products from exons 1 and 10 were electrophoresed on denaturing gradient gels. Main Outcome Measures: Fragments obtained by Southern blot analysis and PCR were compared in patients and controls. Polymerase chain reaction fragments electrophoresed on denaturing gels also were compared in patients and controls. Conclusions: No FSH receptor gene deletions or other mutations were identified in women with POF. Southern blots containing PstI- and HindIII-digested DNA revealed restriction fragment length polymorphisms in both patients and controls. Denaturing gradient gel electrophoresis analysis of PCR fragments of exon 10 also demonstrated DNA sequence polymorphisms in both patients and controls. Follicle-stimulating hormone receptor gene deletions are not common in women with POF, although the gene is polymorphic. We cannot exclude point mutations in other regions of the FSH receptor gene in some patients with POF.