Human testis-expressed (TEX) genes: a review focused on spermatogenesis and male fertility.

Spermatogenesis is a complex process regulated by a multitude of genes. The identification and characterization of male-germ-cell-specific genes is crucial to understanding the mechanisms through which the cells develop. The term "TEX gene" was coined by Wang et al. (Nat Genet. 2001; 27: 422-6) after they used cDNA suppression subtractive hybridization (SSH) to identify new transcripts that were present only in purified mouse spermatogonia. TEX (Testis expressed) orthologues have been found in other vertebrates (mammals, birds, and reptiles), invertebrates, and yeasts. To date, 69 TEX genes have been described in different species and different tissues. To evaluate the expression of each TEX/tex gene, we compiled data from 7 different RNA-Seq mRNA databases in humans, and 4 in the mouse according to the expression atlas database.Various studies have highlighted a role for many of these genes in spermatogenesis. Here, we review current knowledge on the TEX genes and their roles in spermatogenesis and fertilization in humans and, comparatively, in other species (notably the mouse). As expected, TEX genes appear to have a major role in reproduction in general and in spermatogenesis in humans but also in all mammals such as the mouse. Most of them are expressed specifically or predominantly in the testis. As most of the TEX genes are highly conserved in mammals, defects in the male (gene mutations in humans and gene-null mice) lead to infertility. In the future, cumulative data on the human TEX genes' physiological functions and pathophysiological dysfunctions should become available and is likely to confirm the essential role of this family in the reproductive process. Thirteen TEX genes are now referenced in the OMIM database, and 3 have been linked to a specific phenotype. TEX11 (on Xq13.1) is currently the gene most frequently reported as being associated with azoospermia.

RéSUMé: La spermatogenèse est un processus complexe régulé par une multitude de gènes. L'identification et la caractérisation des gènes spécifiques des cellules germinales mâles sont essentielles pour comprendre les mécanismes par lesquels les cellules se développent. Le terme «gène TEX¼ a été inventé par Wang et al. (Nat Genet. 2001; 27: 422­6) après avoir utilisé l'hybridation soustractive d'ADNc (SSH) pour identifier de nouveaux transcrits qui n'étaient présents que dans la spermatogonie de souris. Puis, des orthologues TEX ont été trouvés chez d'autres vertébrés (mammifères, oiseaux et reptiles), des invertébrés et des levures. À ce jour, 69 gènes TEX (Testis expressed) ont été décrits dans différentes espèces et différents tissus. Pour évaluer l'expression de chaque gène TEX/tex, nous avons compilé les données de 7 bases de données différentes d'ARNm RNA-Seq chez l'homme, et 4 chez la souris selon la base de données de l'atlas d'expression.Diverses études ont mis en évidence le rôle de plusieurs de ces gènes dans la spermatogenèse. Ici, nous passons en revue les connaissances actuelles sur les gènes TEX et leurs rôles dans la spermatogenèse et la fécondation chez l'humain et, comparativement, chez d'autres espèces (notamment la souris). Comme prévu, les gènes TEX semblent avoir un rôle majeur dans la reproduction en général et dans la spermatogenèse chez l'homme, mais aussi chez d'autres mammifères comme la souris. La plupart d'entre eux sont exprimés spécifiquement ou principalement dans les testicules. Comme la plupart des gènes TEX sont hautement conservés chez les mammifères, des défauts chez le mâle (mutations géniques chez l'homme et KO murin) conduisent à l'infertilité. À l'avenir, l'accumulation des données sur les fonctions physiologiques et les dysfonctionnements physiopathologiques des gènes TEX humains devraient devenir disponibles et confirmer le rôle essentiel de cette famille dans le processus de reproduction. Treize gènes TEX sont désormais référencés dans la base de données OMIM, et 3 ont été liés à un phénotype spécifique. TEX11 (sur Xq13.1) est. actuellement le gène le plus fréquemment rapporté comme étant associé à l'azoospermie.

Prenatal diagnosis of 2q13 duplications: The crucial role of the family survey in genetic counseling on novel copy number variations.

In recent years, the introduction of novel genome analysis technologies (such as array comparative genomic hybridization) has enabled the prenatal diagnosis of various recurrent copy number variations (CNVs). Some of these CNVs have been linked to a greater susceptibility of developmental and neuropsychiatric disorders; for example, recurrent duplication at the 2q13 locus is associated with developmental delay, dysmorphism and intellectual disability. However, this CNV has low penetrance and variable clinical expressivity. It also can be observed in healthy controls and can be transmitted by unaffected parents, making genetic counseling especially challenging. Here, we report on the inheritance of a 2q13 duplication in an asymptomatic family; the case highlights the role of the family survey in genetic counseling with regard to novel CNVs diagnosed before birth.

A high level of tetrasomy 9p mosaicism but no clinical manifestations other than moderate oligozoospermia with chromosomally balanced sperm: a case report.

Tetrasomy 9p (ORPHA: 3310) (i(9p)) is a rare chromosomal imbalance. It is characterized by the presence of a supernumerary chromosome incorporating two copies of the short arm of chromosome 9 and is usually present in a mosaic state postnatally. Depending on the level of mosaicism, the phenotype ranges from mild developmental delay to multiple congenital anomalies with severe intellectual disability. Here, we report on a patient diagnosed with i(9p) mosaicism after the recurrent failure of in vitro fertilization. Although the patient's clinical phenotype was normal, the level of mosaicism varied greatly from one tissue to another. A sperm analysis evidenced subnormal spermatogenesis with chromosomally balanced spermatozoa and no risk of transmission to the offspring. Although individuals with i(9p) and no clinical manifestations have rarely been described, the prenatal diagnosis of this abnormality in the absence of ultrasound findings raises a number of questions.