A novel missense mutation in the high mobility group domain of SRY drastically reduces its DNA-binding capacity and causes paternally transmitted 46,XY complete gonadal dysgenesis  

Oleh:

Filges, Isabel ; Kunz, Christophe ; Miny, Peter ; Boesch, Nemya

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Fertility and Sterility (keterangan: ada di ClinicalKey) vol. 96 no. 04 (Oct. 2011), page 851-855.
Topik: Swyer syndrome; 46; XY complete gonadal dysgenesis; SRY; gonadal mosaicism; HMG domain; c.347T>C

Ketersediaan

Perpustakaan FK Nomor Panggil: F02.K.2011.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Objective To investigate the familial segregation, role, and function of a novel SRY missense mutation c.347T>C in two half-sisters affected by 46,XY complete gonadal dysgenesis (CDG) compatible with a successful pregnancy outcome. Design Phenotypic, mutational, and functional study. Setting Academic research unit. Patient(s) Two half-sisters, their common father, and 100 healthy control individuals. Intervention(s) Chromosome, molecular cytogenetic analysis, and Sanger sequencing of the SRY gene in blood lymphocytes of the proband, her affected half-sister, and in inflammatory tissue of the father postmortem. Cloning and expression of high mobility group box carboxy-terminal domains of Sry and electrophoretic mobility shift assay were performed. Main Outcome Measure(s) Not applicable. Result(s) A novel SRY missense mutation c.347T>C (p.Leu116Ser) was identified in two half-sisters and segregates with the CGD phenotype. It is present in the common healthy father in a mosaic state. Functional analyses demonstrate the pathogenic effect of the mutation by a strong reduction of DNA affinity for the mutant p.Leu116Ser SRY protein. Conclusion(s) The missense mutation c.347T>C in the high mobility group domain of SRY causes 46,XY CGD. Paternal gonadal mosaicism is likely to explain the familial occurrence of 46,XY CGD suggesting a de novo mutational event during the early stages of embryonic development. This novel mutation is compatible with a successful pregnancy outcome.

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