• PMID: 22441105
• Gene Name: SRY
• Condition: Mixed 46,XY gonadal dysgenesis
• Association: The study reports a case of mixed GD due to a novel SRY point mutation in a patient with a 46,XY karyotype, without mosaicism or submicroscopic genomic imbalances. Hormonal studies showed low anti-müllerian hormone and histological examination of the gona
• Population size: 1
• Population details: 1 46,XY gonadal dysgenesis (GD)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Mixed 46,XY gonadal dysgenesis

A novel SRY mutation leads to asymmetric SOX9 activation and is responsible for mixed 46,XY gonadal dysgenesis

Klee P, Béna F, Birraux J, Dahoun S, Dirlewanger M, Girardin C, Plotton I, Rougemont AL, Morel Y, Schwitzgebel VM.

BACKGROUND: SRY, located on the Y chromosome, is one of the key genes involved in human sex determination. SRY mutations are responsible for 10-15% of all cases of 46,XY gonadal dysgenesis (GD) but are rarely implicated in the pathogenesis of mixed GD. METHODS: SRY was analyzed by sequence analysis of DNA extracted from blood leukocytes. SRY activity was evaluated by SOX9 immunostaining, one of the targets of SRY. RESULTS: We report a case of mixed GD due to a novel SRY point mutation in a patient with a 46,XY karyotype, without mosaicism or submicroscopic genomic imbalances. Hormonal studies showed low anti-müllerian hormone and histological examination of the gonads showed a streak gonad on the right side and a left dysgenetic testis, thus permitting the diagnosis of mixed GD. Immunostaining for SOX9, a target of SRY, was positive in nuclei of Sertoli and epididymal cells in the left gonad and negative on the right, thus indicating asymmetric activation of SRY. CONCLUSION: Mixed GD can result from SRY mutations without mosaicism, neither in peripheral blood, nor within the gonads. The asymmetric effect of the point mutation implies the presence of local factors modulating SRY expression or action. CI - Copyright © 2012 S. Karger AG, Basel. FAU - Klee, Philippe AU - Klee P AD - Endocrine and Diabetes Unit, Department of Pediatrics, University Hospital of Geneva, Geneva, Switzerland. philippe.klee@hcuge.ch FAU - Béna, Frédérique AU - Béna F FAU - Birraux, Jacques AU - Birraux J FAU - Dahoun, Sophie AU - Dahoun S FAU - Dirlewanger, Mirjam AU - Dirlewanger M FAU - Girardin, Céline AU - Girardin C FAU - Plotton, Ingrid AU - Plotton I FAU - Rougemont, Anne-Laure AU - Rougemont AL FAU - Morel, Yves AU - Morel Y