Whole genome sequencing identifies a homozygous splicing variant in TDRKH segregating with non-obstructive azoospermia in an Iranian family - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Clinical Genetics Année : 2024

Whole genome sequencing identifies a homozygous splicing variant in TDRKH segregating with non-obstructive azoospermia in an Iranian family

Nicolas Thierry-Mieg

Résumé

Non‐obstructive azoospermia (NOA) resulting from primary spermatogenic failure represents one of the most severe forms of male infertility, largely because therapeutic options are very limited. Beyond their diagnostic value, genetic tests for NOA also hold prognostic potential. Specifically, genetic diagnosis enables the establishment of genotype‐testicular phenotype correlations, which, in some cases, provide a negative predictive value for testicular sperm extraction (TESE), thereby preventing unnecessary surgical procedures. In this study, we employed whole‐genome sequencing (WGS) to investigate two generations of an Iranian family with NOA and identified a homozygous splicing variant in TDRKH (NM_001083965.2: c.562‐2A>T). TDRKH encodes a conserved mitochondrial membrane‐anchored factor essential for piRNA biogenesis in germ cells. In Tdrkh knockout mice, de‐repression of retrotransposons in germ cells leads to spermatogenic arrest and male infertility. Previously, our team reported TDRKH involvement in human NOA cases through the investigation of a North African cohort. This current study marks the second report of TDRKH 's role in NOA and human male infertility, underscoring the significance of the piRNA pathway in spermatogenesis. Furthermore, across both studies, we demonstrated that men carrying TDRKH variants, similar to knockout mice, exhibit complete spermatogenic arrest, correlating with failed testicular sperm retrieval.
Fichier principal
Vignette du fichier
amiriYekta.clinGenet24.pdf (2.46 Mo) Télécharger le fichier
Origine Publication financée par une institution
Licence

Dates et versions

hal-04633652 , version 1 (03-07-2024)

Licence

Identifiants

Citer

Amir Amiri-Yekta, Sharanya Sen, Florence Hazane-Puch, Célia Tebbakh, Nathalie Roux-Buisson, et al.. Whole genome sequencing identifies a homozygous splicing variant in TDRKH segregating with non-obstructive azoospermia in an Iranian family. Clinical Genetics, In press, ⟨10.1111/cge.14584⟩. ⟨hal-04633652⟩

Collections

TIMC-MAGE
0 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More