Publications by authors named "Zine Eddine Kherraf"
Article Synopsis
- Small RNAs, particularly piRNAs, are essential for male germ cell development, with disruptions leading to male infertility through issues like spermatogenic defects and oligo-astheno-teratozoospermia (OAT).
- The HENMT1 gene is critical for the biogenesis of piRNAs, and its dysfunction can cause severe sperm abnormalities and infertility, as seen in both knockout mice and patients with HENMT1 variants.
- The study aimed to explore the potential for using sperm from two patients with HENMT1 variants in assisted reproductive technologies, but despite thorough analyses and multiple IVF-ICSI attempts, no live births were achieved.
Article Synopsis
- Non-obstructive azoospermia (NOA) from primary spermatogenic failure is a severe male infertility issue with limited treatment options, and genetic testing can help predict outcomes for procedures like testicular sperm extraction (TESE).
- A study using whole-genome sequencing on an Iranian family revealed a harmful variant in the TDRKH gene, which is crucial for male fertility; its absence leads to sperm production failures similar to findings in Tdrkh knockout mice.
- This research reinforces the importance of the piRNA pathway in spermatogenesis and indicates that men with TDRKH variants have a high likelihood of complete spermatogenic arrest, similar to previously studied North African cases.
Article Synopsis
- - A study involving 167 infertile patients identified bi-allelic mutations in the CCDC146 gene, linked to a condition known as multiple morphological abnormalities of the flagellum (MMAF) affecting sperm structure.
- - Researchers developed a knock-out mouse model, which showed that male mice lacking CCDC146 were infertile and had sperm characteristics similar to those of the mutated patients.
- - CCDC146 is important for the proper formation of sperm structures like the axoneme and other microtubule-related organelles, highlighting its role as a microtubule inner protein (MIP) that can lead to infertility when mutated.
Article Synopsis
- Motile cilia and flagella are important organelles involved in movement and are made up of a complex structure called the axoneme, which relies on proteins from numerous genes; defects in these genes can lead to primary ciliary dyskinesia (PCD).
- In a study of 196 infertile men with a specific sperm flagella abnormality known as multiple morphological abnormalities of the flagella (MMAF), researchers identified a harmful variant in the GAS8 gene linked to male infertility.
- The study found that the GAS8 variant disrupts the structure and function of the Nexin-Dynein Regulatory Complex (N-DRC), causing misalignment of microtubules in sperm flagella and resulting in
Article Synopsis
- * Researchers discovered homozygous variants linked to the condition in four unrelated patients, which disrupted the localization of certain proteins essential for sperm flagellum function.
- * The study identified ZMYND12 as a new gene associated with asthenoteratozoospermia, which forms a complex with other proteins critical for sperm motility, affecting male fertility.
Article Synopsis
- The study investigates whether men with specific ultrastructural defects in sperm flagella have lower success rates in intracytoplasmic sperm injection (ICSI) and worse outcomes for pregnancies and newborns.
- A retrospective analysis of 189 ICSI cycles from men with three types of flagellar defects (DFS, PFD, NSFA) was conducted, comparing their outcomes with a control group.
- Results showed no significant negative impact of these defects on fertilization, pregnancy, or delivery rates, indicating generally favorable outcomes despite the presence of flagellar abnormalities.
Article Synopsis
- Sperm fertilization depends on effective movement through the female reproductive system and a process called capacitation, which is influenced by specific signaling pathways.
- Researchers studied an infertile patient with poor sperm motility and found harmful genetic variants affecting proteins related to sperm function.
- The study reveals that these genetic mutations impair sperm's ability to undergo necessary chemical changes for successful fertilization and identifies a crucial protein, IQCH, essential for sperm movement and capacitation.
The use of multigene panel testing for patients with a predisposition to Hereditary Breast and Ovarian Cancer syndrome (HBOC) is increasing as the identification of mutations is useful for diagnosis and disease management. Here, we conducted a retrospective analysis of BRCA1/2 and non-BRCA gene sequencing in 4630 French HBOC suspected patients. Patients were investigated using a germline cancer panel including the 13 genes defined by The French Genetic and Cancer Group (GGC)-Unicancer.
View Article and Find Full Text PDFPrimate-specific genes (PSGs) tend to be expressed in the brain and testis. This phenomenon is consistent with brain evolution in primates but is seemingly contradictory to the similarity of spermatogenesis among mammals. Here, using whole-exome sequencing, we identified deleterious variants of X-linked SSX1 in six unrelated men with asthenoteratozoospermia.
View Article and Find Full Text PDFArticle Synopsis
- Male infertility, specifically the MMAF phenotype, involves severe sperm flagellum defects linked to multiple genetic factors, with around 40 known associated genes.
- In a study of 167 MMAF patients, researchers identified new pathogenic mutations in the DNHD1 gene, previously recognized for its role in this condition, highlighting its crucial function for sperm flagellum structure.
- Advanced imaging techniques confirmed significant abnormalities in sperm cells from mutated patients, reinforcing the importance of understanding these genetic mutations for diagnosing unexplained cases of male infertility.
Article Synopsis
- * Four genes linked to OMD are PATL2, TUBB8, WEE2, and ZP1, with recent studies identifying patients carrying defects in these genes, including a novel ZP1 variant affecting oocyte quality.
- * Whole exome sequencing in a North African cohort revealed that 44% of OMD patients could be diagnosed, highlighting the significant role of genetic testing in understanding female infertility.
Male infertility is an important health concern that is expected to have a major genetic etiology. Although high-throughput sequencing has linked gene defects to more than 50% of rare and severe sperm anomalies, less than 20% of common and moderate forms are explained. We hypothesized that this low success rate could at least be partly due to oligogenic defects - the accumulation of several rare heterozygous variants in distinct, but functionally connected, genes.
View Article and Find Full Text PDFArticle Synopsis
- * This study focuses on enhancing the genetic understanding of NOA by identifying new genes linked to the condition through exome sequencing of 96 individuals who previously tested negative for routine genetic abnormalities.
- * Researchers found potentially causative genetic defects in 16 genes across 22 individuals, with a clear correlation between defects in meiotic genes and unsuccessful sperm retrieval, suggesting that genetic testing could help predict surgical outcomes for patients.
(partner and localizer of ), as indicated by its name, is a -interacting protein that plays an important role in homologous recombination (HR) and DNA double-strand break (DSB) repair. While pathogenic variants of have been well proven to confer an increased risk of breast cancer, data on its involvement in prostate cancer (PrC) have not been clearly demonstrated. We investigated, using targeted next generation sequencing (NGS), a 59-year-old Caucasian man who developed synchronous breast and prostate cancers.
View Article and Find Full Text PDFArticle Synopsis
- In a case study of a man with severe oligozoospermia and a misdiagnosed macrozoospermia, no harmful variants were found in the AURKC gene, prompting the use of WES which identified a harmful variant in the ZMYND15 gene.
- The study confirms that bi-allelic variants in ZMYND15 can cause severe oligozoospermia and may lead to misdiagnosis, emphasizing the importance of using comprehensive genetic testing methods like WES when looking for sperm defect causes.
Article Synopsis
- * Researchers identified two rare loss-of-function variants in testis-specific genes through whole exome sequencing and verified their role using CRISPR/Cas9 to create knockout mice.
- * The knockout mice exhibited normal fertility and sperm parameters, suggesting that the studied genes may not be essential for spermatogenesis, challenging previous assumptions about their role in male fertility.
Article Synopsis
- - Defects in cilia and flagella can lead to serious health issues like primary ciliary dyskinesia (PCD), impacting mainly the respiratory and reproductive systems.
- - A splice variant of the CFAP61 gene, linked to multiple morphological abnormalities of flagella (MMAF), was identified, and knockout mouse models exhibited infertility consistent with this mutation but lacked symptoms typical of PCD.
- - The study shows that CFAP61 is crucial for the stability and structure of flagella, particularly in male reproductive cells, highlighting a specific mechanism that contributes to male infertility.
Article Synopsis
- Oligoasthenoteratozoospermia, a condition leading to male infertility characterized by sperm malformations, has only a few identified pathogenic genes.
- Two homozygous frameshift variants were discovered in patients from China and North Africa, leading to a typical phenotype with low sperm concentration and abnormal sperm flagella structure.
- The research indicates that these genetic mutations are critical for sperm flagella formation and are linked to male infertility in both humans and a created mouse model.
Article Synopsis
- Sperm cells have a head and a flagellum, and problems with the flagellum structure can lead to male infertility, particularly a condition called Multiple Morphological Abnormalities of the Flagella (MMAF).
- Research on a group of infertile men with MMAF revealed that many cases still lack identified causes, but a specific gene called CFAP206 was linked to severe sperm motility defects in one individual.
- Experiments using CRISPR-Cas9 to create mice lacking CFAP206 confirmed that this gene is crucial for proper flagellum function and structure, demonstrating that mutations in CFAP206 can result in male infertility and potential failures in assisted reproductive technologies like ICSI.
Article Synopsis
- Intraflagellar transport (IFT) is critical for forming and maintaining cilia and flagella, with IFT27 being essential for sperm function, as its depletion leads to infertility due to structural and motility issues in sperm.
- LZTFL1, associated with IFT27 and known as BBS17, is linked to Bardet-Biedl syndrome (BBS) and is highly expressed in mouse testis during specific stages of sperm development, particularly close to flagella.
- Lztfl1 knockout mice demonstrated significantly reduced fertility, lower sperm motility, and increased abnormal sperm, with evidence indicating that LZTFL1 plays a vital role in spermatogenesis and male fertility by influencing IFT27 levels.
Article Synopsis
- * A study involving 167 infertile men revealed a specific genetic variant in IFT74 that affects sperm flagellum structure, leading to multiple morphological abnormalities of the sperm flagellum (MMAF).
- * The mutation in IFT74 causes unique protein changes that result in primary male infertility, highlighting how different mutations can lead to distinct clinical outcomes within the broad spectrum of ciliopathies.
Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa.
Caroline Cazin Yasmine Boumerdassi Guillaume Martinez Selima Fourati Ben Mustapha Marjorie Whitfield Zine-Eddine Kherraf
Int J Mol Sci
February 2021
Article Synopsis
- * A study involving nine infertile men from North Africa identified a common genetic variant (c.211+1_211+2dup) in 78% of the participants, which affects a protein essential for sperm structure and function.
- * Despite the genetic mutation, tests showed that sperm from these individuals had normal chromosome numbers, suggesting that assisted reproductive techniques like intra-cytoplasmic sperm injection (ICSI) could be effective, and that