title: A Case of Wiedemann-Steiner Syndrome Associated with a 46,XY Disorder of Sexual Development and Gonadal Dysgenesis.
abstract: We report the case of a female patient suffering from a 46,XY disorder of sexual development (DSD) with complete gonadal dysgenesis and Wiedemann-Steiner Syndrome (WDSTS). The coexistence of these 2 conditions has not yet been reported. Using whole exome sequencing and comparative genome hybridization array, we identified a de novo MLL/KMT2A gene nonsense mutation which explains the WDSTS phenotype. In addition, we discovered novel genetic variants, which could explain the testicular dysgenesis observed in the patient, a maternally inherited 167-kb duplication of DAAM2 and MOCS1 genes and a de novo LRRC33/NRROS gene mutation. These genes, some of which are expressed during mouse gonadal development, could be considered as potentially new candidate genes for DSD.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Calvel
authors.forename: Kamila
authors.initials: K
authors.lastname: Kusz-Zamelczyk
authors.forename: Periklis
authors.initials: P
authors.lastname: Makrythanasis
authors.forename: Damian
authors.initials: D
authors.lastname: Janecki
authors.forename: Christelle
authors.initials: C
authors.lastname: Borel
authors.forename: Béatrice
authors.initials: B
authors.lastname: Conne
authors.forename: Anne
authors.initials: A
authors.lastname: Vannier
authors.forename: Frédérique
authors.initials: F
authors.lastname: Béna
authors.forename: Stefania
authors.initials: S
authors.lastname: Gimelli
authors.forename: Piotr
authors.initials: P
authors.lastname: Fichna
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: Serge
authors.initials: S
authors.lastname: Nef
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Jaruzelska
mesh_terms: D018389:Codon, Nonsense; D019465:Craniofacial Abnormalities / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics; D058490:Disorder of Sex Development, 46,XY / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005835:Genitalia / Q000473:pathology; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008286:Malabsorption Syndromes / Q000235:genetics; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D010375:Pedigree; D013577:Syndrome
chemical_list: D018389:Codon, Nonsense; C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase