Camats Tarruella, Núria; Fernández-Cancio, Mónica; Audí, Laura; Mullis, Primus-Eugen; Moreno, Francisca; González Casado, Isabel; López-Siguero, Juan Pedro; Corripio, Raquel; Bermúdez de la Vega, José Antonio; Blanco, José Antonio; Flück, Christa Emma (2015). Human MAMLD1 Gene Variations Seem Not Sufficient to Explain a 46,XY DSD Phenotype. PLoS ONE, 10(11), e0142831. Public Library of Science 10.1371/journal.pone.0142831
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MAMLD1 is thought to cause disordered sex development in 46,XY patients. But its role is controversial because some MAMLD1 variants are also detected in normal individuals, several MAMLD1 mutations have wild-type activity in functional tests, and the male Mamld1-knockout mouse has normal genitalia and reproduction. Our aim was to search for MAMLD1 variations in 108 46,XY patients with disordered sex development, and to test them functionally. We detected MAMDL1 variations and compared SNP frequencies in controls and patients. We tested MAMLD1 transcriptional activity on promoters involved in sex development and assessed the effect of MAMLD1 on androgen production. MAMLD1 expression in normal steroid-producing tissues and mutant MAMLD1 protein expression were also assessed. Nine MAMLD1 mutations (7 novel) were characterized. In vitro, most MAMLD1 variants acted similarly to wild type. Only the L210X mutation showed loss of function in all tests. We detected no effect of wild-type or MAMLD1 variants on CYP17A1 enzyme activity in our cell experiments, and Western blots revealed no significant differences for MAMLD1 protein expression. MAMLD1 was expressed in human adult testes and adrenals. In conclusion, our data support the notion that MAMLD1 sequence variations may not suffice to explain the phenotype in carriers and that MAMLD1 may also have a role in adult life.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Endokrinologie / Diabetologie / Metabolik (Pädiatrie) 04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pavillon 52 > Endokrinologie / Diabetologie (Erwachsene) |
UniBE Contributor: |
Camats Tarruella, Núria, Mullis, Primus-Eugen, Flück Pandey, Christa Emma |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1932-6203 |
Publisher: |
Public Library of Science |
Language: |
English |
Submitter: |
Anette van Dorland |
Date Deposited: |
22 Mar 2016 10:48 |
Last Modified: |
02 Mar 2023 23:27 |
Publisher DOI: |
10.1371/journal.pone.0142831 |
PubMed ID: |
26580071 |
BORIS DOI: |
10.7892/boris.79272 |
URI: |
https://boris.unibe.ch/id/eprint/79272 |
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