A Human Homologue of the Drosophila melanogaster diaphanous Gene Is Disrupted in a Patient with Premature Ovarian Failure: Evidence for Conserved Function in Oogenesis and Implications for Human Sterility

• DOI: 10.1086/301761
• Publication Date: 2002-07-26T18:45:21Z
• Authors: Silvia Bione; Cinzia Sala; Chiara Manzini; Giulia Arrigo; Orsetta Zuffardi; Sandro Banfi; Giuseppe Borsani; Philippe Jonveaux; Christophe Philippe; Maurizio Zuccotti; Andrea Ballabio; Daniela Toniolo
• Keywords: 570; Ovarian dysgenesis; X Chromosome; X-chromosome rearrangements; Turner syndrome; Molecular Sequence Data; Formins; Primary Ovarian Insufficiency; Translocation, Genetic; 03 medical and health sciences; Oogenesis; Ovarian failure; Amino Acid Sequence; Animals; Carrier Proteins; Chromosome Mapping; Chromosomes, Human, Pair 12; Drosophila melanogaster; Female; Formins; Gene Expression Regulation, Developmental; Humans; Infertility, Female; Molecular Sequence Data; Oogenesis; Ovary; Primary Ovarian Insufficiency; RNA, Messenger; Sequence Homology, Amino Acid; Translocation, Genetic; X Chromosome; Drosophila Proteins; Sterility; Genetics; Animals; Drosophila Proteins; Humans; Genetics(clinical); Amino Acid Sequence; RNA, Messenger; Diaphanous gene; X-chromosome; 0303 health sciences; Chromosomes, Human, Pair 12; Sequence Homology, Amino Acid; Ovary; Chromosome Mapping; Gene Expression Regulation, Developmental; Menopause, early; Oogenesis; Sterility; Menopause; 3. Good health; Drosophila melanogaster; Female; Carrier Proteins; Infertility, Female

Premature ovarian failure (POF) is a defect of ovarian development and is characterized by primary or secondary amenorrhea, with elevated levels of serum gonadotropins, or by early menopause. The disorder has been attributed to various causes, including rearrangements of a large "critical region" in the long arm of the X chromosome. Here we report identification, in a family with POF, of a gene that is disrupted by a breakpoint. The gene is the human homologue of the Drosophila melanogaster diaphanous gene; mutated alleles of this gene affect spermatogenesis or oogenesis and lead to sterility. The protein (DIA) encoded by the human gene (DIA) is the first human member of the growing FH1/FH2 protein family. Members of this protein family affect cytokinesis and other actin-mediated morphogenetic processes that are required in early steps of development. We propose that the human DIA gene is one of the genes responsible for POF and that it affects the cell divisions that lead to ovarian follicle formation.