Heterogeneous nuclear ribonucleoprotein G-T (HNRNP G-T) mutations in men with impaired spermatogenesis

Abstract

The genetic cause of male subfertility due to impaired spermatogenesis is unknown in the majority of cases, but the general assumption is that it is a complex disorder. The aim of this study was to determine whether mutations occur in the HNRNP G-T gene in men with idiopathic impaired spermatogenesis. The heterogeneous nuclear ribonucleoprotein G-T (HNRNP G-T) gene is located in chromosomal region 11p15 that has been shown to be associated with impaired spermatogenesis. It is a member of the hnRNP gene family and is predominantly expressed in pachytene spermatocytes and round spermatids, where it is thought to affect splicing and signal transduction. We identified eight single nucleotide variants in our patient group of 153 subfertile men by sequencing the HNRNP G-T gene. Two of the mutations, R100H and G388del, did not occur in a control group of 143 normozoospermic men. The R100H mutation causes loss of a conserved arginine, thereby affecting a putative site of methylation possibly required for RNA-binding. Interestingly, this mutation was inherited from the mother. The G388del mutation causes loss of one non-conserved glycine located in a glycine stretch at the end of the protein that is not a known functional motif or domain. Our data show that HNRNP G -T mutations are not a frequent cause of impaired spermatogenesis. Nevertheless, the R100H mutation detected suggests that in some men mutations in the HNRNP G-T gene can cause impaired spermatogenesis.

Heterogeneous nuclear ribonucleoprotein A/B and G inhibits the transcription of gonadotropin-releasing-hormone 1

“…reproductive system of males (Delbridge et al, 1999;Ma et al, 1993;Venables et al, 2000;Westerveld et al, 2004). Human hnRNP-G (also named RBMX) gene is coded on the X chromosome and is expressed in many tissues (Lingenfelter et al, 2001) with a differential expression pattern with a characteristic tissue specificity (Nasim et al, 2003) supported in our PCR data in various fish tissues (Fig.…”

Les souris génétiquement modifiées au service de la reproduction

“…Cependant, selon les cohortes de patients étudiés, ces résultats ont été remis en question pour plusieurs de ces gènes [22][23][24]. Seule la démonstration que ces modifications de séquence génétique affecte la fonction du produit du gène concerné pourrait permettre de conclure à une mutation liée à une pathologie.…”

“…Des variations de séquence de HNRNPGT de type mutation « missense » (i.e. « nonsynomymous » ou « point ») (concernant donc un seul nucléotide) ont été identifiées chez des hommes infertiles à partir de l'étude d'une cohorte de 153 patients avec azoospermie ou oligozoospermie sévère [24]. Un homme hétérozygote avec oligoazooteratospermie sévère portait la modification G388del correspondant à une perte d'une glycine.…”

Genetic association study ofRNF8andBRDTvariants with non-obstructive azoospermia in the Chinese Han population

“…Alternatively, the minor C allele of SNP rs2284922 is located in a conserved F-SNP (a web-based SNP analysis tool) sequence [Lee and Shatkay 2008]. A minor alteration of the conserved sequences could induce a phenotypic change [Venkatesh et al 2011;Westerveld et al 2004]. One must also consider that the variation of the SNP rs195434 in the 3 0 -UTR region might affect translational progress, as translational control in the 3 0 -untranslated region (3 0 -UTR) could influence protein level [de Moor et al 2005].…”