A novel hemizygous mutation of MAMLD1 in a patient with 46,XY complete gonadal dysgenesis.

Inge-Lore Ruiz-Arana, Angela Hübner, Cigdem Cetingdag, Heiko Krude, Annette Grüters, Maki Fukami, Heike Biebermann, Birgit Köhler

Journal: Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 2016;9(2):80-5

PMID: 25660412

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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.

Address: Institute for Experimental Paediatric Endocrinology, Charité, Humboldt University Berlin, Berlin, Germany.

DOI: 10.1159/000371603

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MeSH Terms: Adolescent, Amino Acid Sequence, Base Sequence, DNA Mutational Analysis, DNA-Binding Proteins, Disorder of Sex Development, 46,XY, Female, Hemizygote, Humans, Molecular Sequence Data, Mutation, Nuclear Proteins, Promoter Regions, Genetic, Repressor Proteins, Sequence Alignment, Transcription Factors, Transcriptional Activation