Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A novel mutation in FK506 binding protein-like (FKBPL) causes male infertility.

ABSTRACT:

Aim

To perform a mutation analysis of FK506 binding protein-like (FKBPL) in patients with azoospermia.

Methods

DNA samples were isolated from the peripheral blood of 30 azoospermic male patients with normal 46 XY karyotype and 10 healthy controls. Multiplex polymerase chain reaction assays were used to evaluate Y microdeletions, and the patients without deletions were further analyzed. Sanger sequencing was used for mutation analysis.

Results

A heterozygous adenine to guanine substitution was observed at position c.28 (c.28A>G) (one patient), guanine to adenine substitution at c.90 (c.90G>A) (three patients), and a novel insertion mutation of TCTCATAAGTCT at c. 229_240dup (two patients), all in FKBPL exon 2. Furthermore, four different benign variants were observed in the same gene.

Conclusion

Our study supports the literature on the etiologic effects of changes on autosomal chromosomes and highlights the importance of molecular analysis of all known and unknown genes that could be involved in male sexual development and function.

SUBMITTER: Sengun DA

PROVIDER: S-EPMC8275947 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Rimklb mutation causes male infertility in mice.

Project description:Rimklb is a mammalian homologue of the E. coli enzyme RimK, which catalyzes addition of glutamic acid to the ribosomal protein S6. To date, no previous studies have shown any physiological role for Rimklb in mammals. In this study, using Western blotting, we found that Rimklb is distributed and expressed in mouse testis and heart. Rimklb was subsequently localized to the testicular Leydig cells using immunohistochemistry with an anti-Rimklb antibody. We generated a Rimklb mutant mouse in which a three-base deletion results in deletion of Ala 29 and substitution of Leu 30 with Val, which we named the RimklbA29del, L30V mutant mouse. RimklbA29del, L30V mutant mice show a decrease in testicular size and weight, and in vitro fertilization demonstrates complete male infertility. Furthermore, we found that a key factor in the mammalian target of the rapamycin/ribosomal protein S6 transcriptional pathway is hyperphosphorylated in the seminiferous tubules of the mutant testis. We conclude that Rimklb has important roles that include spermatogenesis in seminiferous tubules. In summary, male RimklbA29del, L30V mice are infertile.

| S-EPMC7907349 | biostudies-literature

A novel mutation in PCD-associated gene DNAAF3 causes male infertility due to asthenozoospermia.

Project description:Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive disease manifested with recurrent infections of respiratory tract and infertility. DNAAF3 is identified as a novel gene associated with PCD and different mutations in DNAAF3 results in different clinical features of PCD patients, such as situs inversus, sinusitis and bronchiectasis. However, the sperm phenotypic characteristics of PCD males are generally poorly investigated. Our reproductive medicine centre received a case of PCD patient with infertility, who presented with sinusitis, recurrent infections of the lower airway and severe asthenozoospermia; However, no situs inversus was found in the patient. A novel homozygous mutation in DNAAF3(c.551T>A; p.V184E) was identified in the PCD patient by whole-exome sequencing. Subsequent Sanger sequencing further confirmed that the DNAAF3 had a homozygous missense variant in the fifth exon. Transmission electron microscopy and immunostaining analysis of the sperms from the patient showed a complete absence of outer dynein arms and partial absence of inner dynein arms, which resulted in the reduction in sperm motility. However, this infertility was overcome by intracytoplasmic sperm injections, as his wife achieved successful pregnancy. These findings showed that the PCD-associated pathogenic mutation within DNAAF3 also causes severe asthenozoospermia and male infertility ultimately due to sperm flagella axoneme defect in humans. Our study not only contributes to understand the sperm phenotypic characteristics of patients with DNAAF3 mutations but also expands the spectrum of DNAAF3 mutations and may contribute to the genetic diagnosis and therapy for infertile patient with PCD.

| S-EPMC10568663 | biostudies-literature

Genetic causes of male infertility.

Project description: Not available

| S-EPMC3776680 | biostudies-literature

Fam170a deficiency causes male infertility

Project description:During spermiogenesis, nucleus condensation packages genomic DNA into tiny sperm heads by histone-to-protamine chromatin remodeling process, which is essential to male fertility. However, this process involving key events and regulators is still poorly understood. Herein, we report that Fam170a orchestrates the histone-to-protamine chromatin remodeling process by interacting with its associated proteins and mediating its associated gene expression.

2024-11-10 | GSE280742 | GEO

A novel hemizygous loss-of-function mutation in ADGRG2 causes male infertility with congenital bilateral absence of the vas deferens.

Project description:PurposeCystic fibrosis transmembrane conductance regulator (CFTR) and adhesion G protein-coupled receptor G2 (ADGRG2) have been identified as the main pathogenic genes in congenital bilateral absence of the vas deferens (CBAVD), which is an important cause of obstructive azoospermia. This study aimed to identify the disease-causing gene in two brothers with CBAVD from a Chinese consanguineous family and reveal the intracytoplasmic sperm injection (ICSI) outcomes in these patients.MethodsWhole-exome sequencing and Sanger sequencing were used to identify the candidate pathogenic genes. Real-time polymerase chain reaction, immunohistochemistry, and immunofluorescence were used to assess the expression of the mutant gene. Moreover, the ICSI results from both patients were retrospectively reviewed.ResultsA novel hemizygous loss-of-function mutation (c.G118T: p.Glu40*) in ADGRG2 was identified in both patients with CBAVD. This mutation is absent from the human genome databases and causes an early translational termination in the third exon of ADGRG2. Expression analyses showed that both the ADGRG2 mRNA and the corresponding protein were undetectable in the proximal epididymal tissue of ADGRG2-mutated patients. ADGRG2 expression was restricted to the apical membranes of non-ciliated epithelia in human efferent ducts, which was consistent with a previous report in mice. Both ADGRG2-mutated patients had normal spermatogenesis and had successful clinical outcomes following ICSI.ConclusionsOur study verifies the pathogenic role of ADGRG2 in X-linked CBAVD and broadens the spectrum of ADGRG2 mutations. In addition, we found positive ICSI outcomes in the two ADGRG2-mutated CBAVD patients.

| S-EPMC7311603 | biostudies-literature

Human male infertility and its genetic causes.

Project description:BackgroundInfertility affects about 15% of couples who wish to have children and half of these cases are associated with male factors. Genetic causes of azoospermia include chromosomal abnormalities, Y chromosome microdeletions, and specific mutations/deletions of several Y chromosome genes. Many researchers have analyzed genes in the AZF region on the Y chromosome; however, in 2003 the SYCP3 gene on chromosome 12 (12q23) was identified as causing azoospermia by meiotic arrest through a point mutation.MethodsWe mainly describe the SYCP3 and PLK4 genes that we have studied in our laboratory, and add comments on other genes associated with human male infertility.ResultsUp to now, The 17 genes causing male infertility by their mutation have been reported in human.ConclusionsInfertility caused by nonobstructive azoospermia (NOA) is very important in the field of assisted reproductive technology. Even with the aid of chromosomal analysis, ultrasonography of the testis, and detailed endocrinology, only MD-TESE can confirm the presence of immature spermatozoa in the testes. We strongly hope that these studies help clinics avoid ineffective MD-TESE procedures.

| S-EPMC5661822 | biostudies-literature

Haploinsufficiency of kelch-like protein homolog 10 causes infertility in male mice.

Project description:We identified a testis-specific gene encoding a protein containing a BTB/POZ domain and six kelch repeats, which we named kelch homolog 10 (KLHL10). KLHL10 displays high evolutionary conservation in mammals, as evidenced by 98.7% amino acid identity between mouse and human KLHL10. KLHL10 is exclusively expressed in the cytoplasm of elongating and elongated spermatids (steps 9-16). We generated a Klhl10 null allele in 129S6/SvEv mouse embryonic stem cells, and obtained 47 chimeras from six independent embryonic stem cell lines. Whereas low-percentage male chimeras only produce C57BL/6J offspring, high-percentage chimeric and heterozygous males were completely infertile because of disrupted spermiogenesis characterized by asynchronous spermatid maturation, degeneration of late spermatids, sloughing of postmeiotic germ cells from the seminiferous epithelium, and marked reduction in the numbers of late spermatids. Our data demonstrate that, like protamine-1 and -2, both alleles of Klhl10 are required for male fertility and that haploinsufficiency caused by a mutation in one allele of Klhl10 prevents genetic transmission of both mutant and WT alleles.

| S-EPMC419685 | biostudies-literature

Loss of polyadenylation protein tauCstF-64 causes spermatogenic defects and male infertility.

Project description:Polyadenylation, the process of eukaryotic mRNA 3' end formation, is essential for gene expression and cell viability. Polyadenylation of male germ cell mRNAs is unusual, exhibiting increased alternative polyadenylation, decreased AAUAAA polyadenylation signal use, and reduced downstream sequence element dependence. CstF-64, the RNA-binding component of the cleavage stimulation factor (CstF), interacts with pre-mRNAs at sequences downstream of the cleavage site. In mammalian testes, meiotic XY-body formation causes suppression of X-linked CstF-64 expression during pachynema. Consequently, an autosomal paralog, tauCstF-64 (gene name Cstf2t), is expressed during meiosis and subsequent haploid differentiation. Here we show that targeted disruption of Cstf2t in mice causes aberrant spermatogenesis, specifically disrupting meiotic and postmeiotic development, resulting in male infertility resembling oligoasthenoteratozoospermia. Furthermore, the Cstf2t mutant phenotype displays variable expressivity such that spermatozoa show a broad range of defects. The overall phenotype is consistent with a requirement for tauCstF-64 in spermatogenesis as indicated by the significant changes in expression of thousands of genes in testes of Cstf2t(-/-) mice as measured by microarray. Our results indicate that, although the infertility in Cstf2t(-/-) males is due to low sperm count, multiple genes controlling many aspects of germ-cell development depend on tauCstF-64 for their normal expression. Finally, these transgenic mice provide a model for the study of polyadenylation in an isolated in vivo system and highlight the role of a growing family of testis-expressed autosomal retroposed variants of X-linked genes.

| S-EPMC2154438 | biostudies-literature

FK506-binding protein 51 is a possible novel tumoral marker.

Project description: Not available

| S-EPMC3032557 | biostudies-literature