De novo mutations in idiopathic male infertility ‐ a pilot study

AbstractStudy questionAre de novo mutations in the human genome associated with male infertility?Summary answerWe identified de novo mutations in five candidate genes: SEMA5A, NEURL4, BRD2, CD1D, and CD63.What is known alreadyEpidemiological and genetic studies have consistently indicated contribution of genetic factors to the etiology of male infertility, suggesting that more than 1500 genes are involved in spermatogenesis.Study design, size, durationFirst we searched for de novo mutations in patients with idiopathic azoospermia with whole exome sequencing (WES). To evaluate the potential functional impact of de novo identified mutations we analyzed their expression differences on independent testis samples with normal and impaired spermatogenesis. In the next step we tested additional group of azoospermic patients for mutations in identified genes with de novo mutations. In addition to the analysis of de novo mutations in patients with idiopathic azoospermia, we considered other models of inheritance and searched for candidate genes harboring rare maternally inherited variants and biallelic autosomal and X ‐chromosome hemizygous variants.Participants/materials, setting, methodsWe performed WES in 13 infertile males with idiopathic azoospermia and their parents. Potential functional impact of de novo identified mutations was evaluated by global gene ‐expression profiling on 20 independent testis samples. To replicate the results we performed WES in further 16 independent...
Source: Andrology - Category: Urology & Nephrology Authors: Tags: ORIGINAL ARTICLE Source Type: research