Additional evidence for the role of chromosomal imbalances and SOX8, ZNRF3 and HHAT gene variants in early human testis development.
Reprod Biol Endocrinol
; 21(1): 2, 2023 Jan 11.
Article
en En
| MEDLINE
| ID: mdl-36631813
ABSTRACT
BACKGROUND:
Forty-six ,XY Differences/Disorders of Sex Development (DSD) are characterized by a broad phenotypic spectrum ranging from typical female to male with undervirilized external genitalia, or more rarely testicular regression with a typical male phenotype. Despite progress in the genetic diagnosis of DSD, most 46,XY DSD cases remain idiopathic.METHODS:
To determine the genetic causes of 46,XY DSD, we studied 165 patients of Tunisian ancestry, who presented a wide range of DSD phenotypes. Karyotyping, candidate gene sequencing, and whole-exome sequencing (WES) were performed.RESULTS:
Cytogenetic abnormalities, including a high frequency of sex chromosomal anomalies (85.4%), explained the phenotype in 30.9% (51/165) of the cohort. Sanger sequencing of candidate genes identified a novel pathogenic variant in the SRY gene in a patient with 46,XY gonadal dysgenesis. An exome screen of a sub-group of 44 patients with 46,XY DSD revealed pathogenic or likely pathogenic variants in 38.6% (17/44) of patients.CONCLUSION:
Rare or novel pathogenic variants were identified in the AR, SRD5A2, ZNRF3, SOX8, SOX9 and HHAT genes. Overall our data indicate a genetic diagnosis rate of 41.2% (68/165) in the group of 46,XY DSD.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Testículo
/
Aciltransferasas
/
Ubiquitina-Proteína Ligasas
/
Desarrollo Sexual
/
Factores de Transcripción SOXE
/
Disgenesia Gonadal 46 XY
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
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Male
Idioma:
En
Revista:
Reprod Biol Endocrinol
Asunto de la revista:
ENDOCRINOLOGIA
/
MEDICINA REPRODUTIVA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Túnez