FOLLICLE-STIMULATING-HORMONE BETA-GENE STRUCTURE IN PREMATURE OVARIANFAILURE

Objective: To determine whether mutations in the gene for FSHbeta are present, and possibly etiologic, in some patients with 46,XX premature ovarian failure (POF). Design: DNA samples obtained from 18 study pat ients with POF and two menopausal fertile controls were studied by Sou thern blot analysis. DNA sequencing was performed in one patient. Sett ing: Patients were seen in a reproductive endocrinology clinic and stu died in a medical school laboratory setting at the Medical College of Georgia and Tufts University. Main Outcome Measures: Restriction fragm ent sizes on autoradiographs were compared between the study group and controls. DNA sequencing radiographs were compared between one study patient and five controls. Results: Fragment sizes obtained with the r estriction enzymes EcoRI, DraI, HincII, PstI, KpnI, BglI, BamHI, and B glII were similar size in both study subjects and controls using the p robes pFSHbeta-1.4 and pFSHbeta-1.2. A previously described HindIII po lymorphism was present using pFSHbeta-1.2, but HindIII fragment sizes were identical in patients with ovarian failure and controls using pFS Hbeta-1.4. DNA sequencing of the FSHbeta gene in one patient was norma l. Conclusions: No mutations in the gene for FSHbeta were identified i n women with POF. DNA sequencing of the exons and promoter region of t he FSHbeta gene in one woman with POF was normal. This does not entire ly exclude the possibility that smaller deletions, insertions, or poin t mutations of the FSHbeta could be etiologic in some women with POF. The HindIII polymorphism does not appear to segregate with 46,XX POF.