Genetic Architecture of Azoospermia-Time to Advance the Standard of Care.

Background: Crypto- and azoospermia (very few/no sperm in the semen) are main contributors to male factor infertility. Genetic causes for spermatogenic failure (SPGF) include Klinefelter syndrome and Y-chromosomal azoospermia factor microdeletions, and CFTR mutations for obstructive azoospermia (OA). However, the majority of cases remain unexplained because monogenic causes are not analysed.

Sequence Variants in TBX6 Are Associated with Disorders of the Müllerian Ducts: An Update.

Müllerian anomalies comprise the Mayer-Rokitansky-Küster-Hauser syndrome as well as fusion defects of the müllerian ducts. Recurrent micro-aberrations like deletions in 16p11.2 encompassing TBX6 were found to be causative in these patients.

Four Novel NR5A1 Mutations in 46,XY Gonadal Dysgenesis Patients Including Frameshift Mutations with Altered Subcellular SF-1 Localization.

46,XY gonadal dysgenesis (46,XY GD) is a disorder of sexual development caused by mutations in genes involved in early gonadal development (bipotential gonads) and testis differentiation. In 46,XY GD individuals, mutations of the SRY gene are detected most frequently, followed by mutations in the NR5A1 (SF-1) gene, but in a lot of cases, the underlying molecular mechanism remains elusive. In this study, we retrospectively performed sequence analyses of the NR5A1 (SF-1) gene in 84 patients with complete, partial, and syndromic forms of 46,XY GD.

Variations in RBM8A and TBX6 are associated with disorders of the müllerian ducts.

Objective: To identify genetic causes of malformations of the müllerian ducts.

Design: Retrospective laboratory study.

Setting: University hospital.

DMRT1 mutations are rarely associated with male infertility.

Objective: To study a potential association between male infertility and DMRT1 mutations.

Design: Retrospective sequencing study.

Setting: University hospital.

Comprehensive sequence analysis of the NR5A1 gene encoding steroidogenic factor 1 in a large group of infertile males.

The steroidogenic factor 1 (SF1) protein, encoded by the NR5A1 gene, plays a central role in gonadal development and steroidogenesis. Mutations in NR5A1 were first described in patients with primary adrenal insufficiency and 46,XY disorders of sexual development and later also in men with hypospadias, bilateral anorchia and micropenis and women with primary ovarian insufficiency. Recently, heterozygous missense mutations were found in 4% of infertile men with unexplained reduced sperm counts living in France, but all mutation carriers were of non-Caucasian ancestry.