title: Isolated hypogonadotropic hypogonadism with SOX2 mutation and anophthalmia/microphthalmia in offspring.
abstract: Isolated hypogonadotropic hypogonadism (IHH) is a genetically heterogeneous condition in which patients frequently require assisted reproduction to achieve fertility. In patients with IHH who are otherwise well, no particular increased risk of congenital anomalies in the resultant offspring has been highlighted. Heterozygous mutations in SOX2 are the commonest single-gene cause of anophthalmia/microphthalmia (A/M) and sometimes result in pituitary abnormalities. We report a family with a novel frameshift mutation in the SOX2 transactivation domain, p.Gly280AlafsX91, resulting in bilateral anophthalmia and subtle endocrinological abnormalities in a male sibling, and unilateral microphthalmia in a female sibling. The mutation is present in their mother who has IHH, but has no eye disorders or other anomalies. She underwent assisted reproduction to achieve fertility. This report has important implications for the evaluation of patients with IHH, particularly in the setting of planned infertility treatment.
authors.affiliation: Genetic Health Services Victoria, and Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
authors.forename: Zornitza
authors.initials: Z
authors.lastname: Stark
authors.forename: Rebecca
authors.initials: R
authors.lastname: Storen
authors.forename: Bruce
authors.initials: B
authors.lastname: Bennetts
authors.forename: Ravi
authors.initials: R
authors.lastname: Savarirayan
authors.forename: Robyn V
authors.initials: RV
authors.lastname: Jamieson
mesh_terms: D000328:Adult; D000853:Anophthalmos / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000473:pathology; D002648:Child; D005260:Female; D006579:Heterozygote; D006801:Humans; D007006:Hypogonadism / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D055748:SOXB1 Transcription Factors / Q000235:genetics*
chemical_list: C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors