Novel Inactivating Mutation of the FSH Receptor in Two Siblings of Indian Origin With Premature Ovarian Failure

Abstract

Both daughters were found to have a novel pathogenic variant in FSHR (c.1253T>G, p.Ile418Ser), inherited as an autosomal recessive trait from heterozygous parents. This loss of function mutation is located in exon 10 of FSHR affecting the second transmembrane helix of the FSHR protein. The transmembrane domain of FSHR is highly conserved across species and is involved in signal transduction. The FSHR c.1253T>G variant is next to a known pathogenic variant, rs12190966 (c.1255G>A, p.Ala419Thr), previously reported in a Finnish woman with primary amenorrhea.