title: A novel hemizygous mutation of MAMLD1 in a patient with 46,XY complete gonadal dysgenesis.
abstract: MAMLD1 is suggested to play a role in the development of 46,XY disorders of sexual development (46,XY DSD). So far, mutations in this gene have been detected in several cases of hypospadias with normal testosterone levels at birth. From in vitro studies it was concluded that Mamld1 might transiently affect testosterone synthesis during genital development. We describe the first MAMLD1 mutation in a 46,XY patient with complete gonadal dysgenesis. The novel MAMLD1 missense mutation (p.P677L) results in a severely reduced transactivation in vitro of the promoter of the MAMLD1 target gene HES3/Hes3. However, as knowledge about the functional role of MAMLD1 in gonadal development is limited, we suggest that additional factors (digenic or oligogenic cause) play a role in the development of complete gonadal dysgenesis in this patient.
authors: Institute for Experimental Paediatric Endocrinology, Charité, Humboldt University Berlin, Berlin, Germany.
authors: Inge-Lore
authors: IL
authors: Ruiz-Arana
authors: Angela
authors: A
authors: Hübner
authors: Cigdem
authors: C
authors: Cetingdag
authors: Heiko
authors: H
authors: Krude
authors: Annette
authors: A
authors: Grüters
authors: Maki
authors: M
authors: Fukami
authors: Heike
authors: H
authors: Biebermann
authors: Birgit
authors: B
authors: Köhler
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D058490:Disorder of Sex Development, 46,XY / Q000235:genetics*; D005260:Female; D057898:Hemizygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C495457:HES3 protein, human; C528016:MAMLD1 protein, human; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors