Follicle-stimulating hormone beta gene structure in premature ovarian failure

To determine whether mutations in the gene for FSHβ are present, and possibly etiologic, in some patients with 46,XX premature ovarian failure (POF). DNA samples obtained from 18 study patients with POF and two menopausal fertile controls were studied by Southern blot analysis. DNA sequencing was performed in one patient. Patients were seen in a reproductive endocrinology clinic and studied in a medical school laboratory setting at the Medical College of Georgia and Tufts University. Restriction fragment sizes on autoradiographs were compared between the study group and controls. DNA sequencing radiographs were compared between one study patient and five controls. Fragment sizes obtained with the restriction enzymes EcoRI, DraI, HincII, PstI, KpnI, BglI, BamHI, and BglII were similar size in both study subjects and controls using the probes pFSHβ-1.4 and pFSHβ-1.2. A previously described HindIII polymorphism was present using pFSHβ-1.2, but HindIII fragment sizes were identical in patients with ovarian failure and controls using pFSHβ-1.4. DNA sequencing of the FSHβ gene in one patient was normal. No mutations in the gene for FSHβ were identified in women with POF. DNA sequencing of the exons and promoter region of the FSHβ gene in one woman with POF was normal. This does not entirely exclude the possibility that smaller deletions, insertions, or point mutations of the FSHβ could be etiologic in some women with POF. The HindIII polymorphism does not appear to segregate with 46,XX POF.