Publications by authors named "Selima Fourati Ben Mustapha"
Asthenoteratozoospermia is a common cause of male infertility. To further define the genetic causes underlying asthenoteratozoospermia, we performed whole-exome sequencing in a cohort of Han Chinese men with asthenoteratozoospermia. Homozygous deleterious variants of MYCBPAP were first identified in two unrelated Chinese cases.
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- 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
- - 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
- * 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
- * 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.
Article 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.
Combined Use of Whole Exome Sequencing and CRISPR/Cas9 to Study the Etiology of Non-Obstructive Azoospermia: Demonstration of the Dispensable Role of the Testis-Specific Genes and .
Caroline Cazin Yasmine Neirijnck Corinne Loeuillet Lydia Wehrli Françoise Kühne Selima Fourati Ben Mustapha
Cells
December 2021
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.
Correction to: A missense mutation in IFT74, encoding for an essential component for intraflagellar transport of Tubulin, causes asthenozoospermia and male infertility without clinical signs of Bardet-Biedl syndrome.
Patrick Lorès Zine-Eddine Kherraf Amir Amiri-Yekta Marjorie Whitfield Abbas Daneshipour Selima Fourati Ben Mustapha
Hum Genet
July 2021
A missense mutation in IFT74, encoding for an essential component for intraflagellar transport of Tubulin, causes asthenozoospermia and male infertility without clinical signs of Bardet-Biedl syndrome.
Patrick Lorès Zine-Eddine Kherraf Amir Amiri-Yekta Marjorie Whitfield Abbas Daneshipour Selima Fourati Ben Mustapha
Hum Genet
July 2021
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.
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
Article Synopsis
- Globozoospermia is a type of male infertility characterized by round-headed sperm that lack an acrosome, with genetic anomalies in the DPY19L2 gene accounting for 50-70% of cases, often due to complete gene deletions.* -
- A study involving 69 patients found that 36% had homozygous deletions of the DPY19L2 gene, and even higher proportions of genetic defects correlated with increased rates of globozoospermia, indicating a strong relationship between genotype and phenotype.* -
- The study suggests a new diagnostic approach focusing on patients with over 50% globozoospermia by initially testing for DPY19L2 deletions using
Article Synopsis
- The COVID-19 pandemic presents a challenge for Reproductive Medicine, which is typically considered a non-emergency activity, except for cases involving cancer-related fertility preservation.
- Leading fertility organizations like ASRM and ESHRE advised halting new patient intakes and suggested continuing only existing IVF cycles with a preference for Freeze-all strategies.
- Recent developments and new data have emerged, prompting a need to revise previously established recommendations in Tunisia, reflecting the changes in the situation.
Article Synopsis
- Structural defects in sperm flagella lead to asthenozoospermia, a common issue in infertile men, particularly seen as "short tails" (MMAF).
- Research on 167 individuals with MMAF revealed that over 30% had harmful mutations, notably in the TTC29 gene, which is crucial for sperm flagellar function.
- Further studies in model organisms confirmed that TTC29 is vital for maintaining proper sperm flagellum structure and movement, linking its mutations to male infertility.
Article Synopsis
- Multiple morphological anomalies of the sperm flagella (MMAF syndrome) is a serious cause of male infertility linked to mutations in several genes that affect sperm flagellum structure.
- Research identified significant homozygous mutations in the QRICH2 gene, crucial for sperm flagellum development, in patients from two Chinese families and further analyzed a wider cohort to link QRICH2 to MMAF.
- Out of 167 affected individuals, 1% had homozygous loss-of-function variants confirming QRICH2's role, while 9.6% had heterozygous variants, suggesting these variants are common and not specifically linked to MMAF syndrome.
Article Synopsis
- Male infertility is a significant health issue, with multiple morphological abnormalities of the flagella (MMAF) being a severe form that causes asthenozoospermia due to irregular sperm flagella.
- Six genes linked to MMAF have been identified; however, many cases remain unexplained, indicating more undiscovered gene defects.
- Whole-exome sequencing revealed that mutations in the ARMC2 gene cause the MMAF phenotype in both humans and mice, highlighting its crucial role in sperm flagellum structure and assembly.
Article Synopsis
- * Previous studies identified that mutations in genes like DNAH1 and CFAP43/44 account for about one-third of MMAF cases, suggesting there are still more genes to discover.
- * The study included genetic analyses and tissue examinations to characterize sperm abnormalities associated with these mutations, highlighting the importance of the FSIP2 gene in sperm development.
Article Synopsis
- Multiple morphological abnormalities of the sperm flagellum (MMAF) is a serious male infertility issue characterized by various sperm flagella defects, linked to genetic mutations affecting axonemal proteins.
- Researchers analyzed whole-exome sequencing data from 78 affected individuals and discovered a homozygous deletion in the WDR66 gene in 7 cases, indicating a new genetic contributor to MMAF.
- Further experiments, including studies on a related protein in Trypanosoma, demonstrated that this gene deletion impairs flagellar movement, thus confirming WDR66's role in male infertility related to MMAF.
Article Synopsis
- The genetic basis of oocyte meiotic deficiency (OMD), a primary infertility issue linked to immature egg production, is under-researched.
- A study using whole exome sequencing revealed that 26% of individuals with OMD carried the same harmful mutation in the PATL2 gene, which is thought to be crucial for RNA regulation.
- Experiments with knockout mice indicated that the absence of PATL2 disrupts oocyte development and maturation by affecting key gene expressions, establishing PATL2 as an important factor in mammalian fertility.
Article Synopsis
- Spermatogenesis issues affect millions of men globally, but many remain undiagnosed.
- The research identified 22 men with primary infertility linked to mutations in genes DNAH1, CFAP43, and CFAP44, confirmed through genetic sequencing.
- CRISPR/Cas9 experiments on mice demonstrated that CFAP43 and CFAP44 are crucial for producing functional sperm flagella, underscoring their importance across different species.
Article Synopsis
- The study investigates whether mutations in the DNAH1 gene affect outcomes of intracytoplasmic sperm injection (ICSI) in patients with multiple morphological abnormalities of the sperm flagella (MMAF).
- Findings indicate that despite significant sperm abnormalities, MMAF patients with DNAH1 mutations exhibit low aneuploidy rates and good nuclear quality, resulting in high embryonic development success and pregnancy rates after ICSI.
- This retrospective cohort study analyzed data from 6 MMAF patients with DNAH1 mutations compared to two control groups, demonstrating that genetic factors can influence ICSI efficacy in men with sperm morphology defects.
Article Synopsis
- The study examines the role of the testicular isoform of angiotensin converting enzyme (tACE) in male fertility, particularly its impact on sperm binding to the zona pellucida (ZP) during fertilization, drawing parallels to findings in mice.
- In the study, 24 men with similar normal semen parameters were analyzed, with 10 experiencing IVF failures and no sperm binding to the ZP, while 14 had successful fertilization.
- Results revealed that 3 of the unsuccessful cases and 1 control had no tACE expression, but no genetic mutations were found, indicating that tACE does not play a significant role in human fertilization or ZP binding.