Identification of a new<i>DPY19L2</i>mutation and a better definition of<i>DPY19L2</i>deletion breakpoints leading to globozoospermia

Ghédir, Houda; Ibala-Romdhane, Samira; Okutman, Özlem; Viot, Géraldine; Saâd, Ali; Viville, Stéphane

doi:10.1093/molehr/gav061

Cited by 38 publications

(42 citation statements)

References 27 publications

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“…For these patients, an absolute teratozoospermia (100% abnormal morphology) with a total globozoospermia phenotype (100% round‐headed acrosomeless spermatozoa) was diagnosed. For six patients, homozygous deletion of the entire DPY19L2 was confirmed in our previous work (Ghedir et al, ). For all patients, there was no history of radiotherapy, chemotherapy, orchitis, toxic exposure, trauma, varicocele, testicular torsion, chronic illness or medication.…”

Section: Methodssupporting

confidence: 69%

“…Currently, two genes are known to be associated with total human globozoospermia: DPY19L2 (Dpy‐19 Like 2) and SPATA16 (Spermatogenesis associated 16) . The deletion of the entire DPY19L2 gene was found in the majority of globozoospermic patients reported in the literature and thus considered as the main cause of total globozoospermia (Ghedir et al, ; Harbuz et al, ; Koscinski et al, ). While in SPATA16 gene, one familial mutation (c.848G>A/p.R283Q) (Dam, Koscinski, et al, ) and a new deletion of exon 2 (ElInati et al, ) were identified in only two patients.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of sperm morphology and nuclear sperm quality in SPATA16‐ and DPY19L2‐ mutated globozoospermic patients

et al. 2019

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The aim of this study was to compare the sperm morphology and nuclear sperm quality (sperm aneuploidy and DNA fragmentation) in two groups of globozoospermic patients: DPY19L2‐mutated patients (n = 6) and SPATA16‐mutated patients (n = 2). Results for these two groups were also compared to a group of fertile men (n = 25). Fluorescence in situ hybridisation was performed for chromosomes X, Y and 18. Sperm DNA fragmentation was evaluated by TUNEL assay. Sanger sequencing was performed for mutations screening of DPY19L2 and SPATA16 genes. Sperm analysis revealed a classic phenotype of total globozoospermia in DPY19L2‐mutated group and a particular phenotype characterised by a predominance of double/multiple round‐headed (39.00 ± 4.2%) and multi‐tailed spermatozoa (26.00 ± 16.97%) in SPATA16‐mutated group. FISH analysis showed a significantly higher aneuploidy rate in globozoospermic patients compared to controls (p < 0.05), and a higher rate was observed in SPATA16‐mutated group compared to DPY19L2‐mutated group (p < 0.05). DNA fragmentation index was significantly higher in globozoospermic men compared to controls (p < 0.001), and there is no statistically significant difference between the two globozoospermic groups. We showed that SPATA16 defects could be associated with an abnormal meiosis leading to a particular morphological sperm defect of double/multiple round‐headed and multi‐flagella and a higher sperm aneuploidy rate than in case of DPY19L2‐defects in classic globozoospermia.

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Section: Methodssupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Comparison of sperm morphology and nuclear sperm quality in SPATA16‐ and DPY19L2‐ mutated globozoospermic patients

et al. 2019

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“…Four additional studies confirmed the high prevalence of DPY19L2 gene alterations, ranging from 60 to 83.3% of analyzed patients in cohorts of globozoospermic patients from different geographic origin (58)(59)(60)(61). Homozygous deletions represent the major mutational event with 26.7 to 73.3% of the reported DPY19L2 mutations in these four largest studies (58)(59)(60)(61). Two other studies on smaller groups of two Macedonian and five Algerian patients reinforced this conclusion with the presence of homozygous DPY19L2 deletion in all analyzed patients (30,62).…”

Section: Globozoospermiamentioning

confidence: 66%

“…Indeed, DPY19L2 screening will most often result in a negative outcome in cohort with a low percentage of globozoospermia (28). Considering all studies with a full DPY19L2 gene screening, DPY19L2 alterations are found in 70.2% of all 131 analyzed globozoospermic-unrelated patients with the homozygous deletion found in 52.3% (28,30,55,(58)(59)(60)(61)(62). Overall, the recurrent genomic deletion of the DPY19L2 gene represents 80.4% of the pathological alleles (148 out of 184) ( Fig.…”

Section: Globozoospermiamentioning

confidence: 99%

Genetic abnormalities leading to qualitative defects of sperm morphology or function

et al. 2016

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Infertility, defined by the inability of conceiving a child after 1 year is estimated to concern approximately 50 million couples worldwide. As the male gamete is readily accessible and can be studied by a simple spermogram it is easier to subcategorize male than female infertility. Subjects with a specific sperm phenotype are more likely to have a common origin thus facilitating the search for causal factors. Male infertility is believed to be often multifactorial and caused by both genetic and extrinsic factors, but severe cases of male infertility are likely to have a predominant genetic etiology. Patients presenting with a monomorphic teratozoospermia such as globozoospermia or macrospermia with more than 85% of the spermatozoa presenting this specific abnormality have been analyzed permitting to identify several key genes for spermatogenesis such as AURKC and DPY19L2. The study of patients with other specific sperm anomalies such as severe alteration of sperm motility, in particular multiple morphological anomalies of the sperm flagella (MMAF) or sperm unability to fertilize the oocyte (oocyte activation failure syndrome) has also enable the identification of new infertility genes. Here we review the recent works describing the identification and characterization of gene defects having a direct qualitative effect on sperm morphology or function.

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“…Globozoospermia is a rare (prevalence of <0.1%) but severe fertility disorder characterized by round-headed spermatozoa with malformed acrosomes or a complete lack of acrosomes [1]. According to the percentage of round-headed and acrosomeless spermatozoa per ejaculate, globozoospermia can be classified as classic/total globozoospermia (100%) or partial globozoospermia (<100%) [2].…”

Section: Introductionmentioning

confidence: 99%

Decreased Expression of KIFC1 in Human Testes with Globozoospermic Defects

Zhi

Chen

et al. 2016

Genes

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Globozoospermia is a rare (prevalence of <0.1%) but severe male infertility condition. In our previous study, we found that robust KIFC1 immunostaining was detected in the human elongating/elongated spermatids during human acrosomogenesis. However, the relationship between the decreased expression of KIFC1 and human globozoospermia remains largely unknown. Testicular biopsies of 30 globozoospermia and 30 obstructive azoospermia patients who underwent infertility evaluation and treatment were utilized in this study. Reverse transcriptase polymerase chain reaction (RT-PCR), Western blots, immunohistochemistry, an in vivo model, and intratesticular injection of small inhibitory RNA (siRNA) against the Kifc1 gene were employed, and sperm abnormalities were evaluated by hematoxylin and eosin (H&E) staining and immunocytochemistry. We revealed that the testicular level of KIFC1 mRNA in globozoospermia was significantly reduced compared with that in obstructive azoospermia, and the KIFC1 protein was barely detectable in testicular specimens in 30% (9 of 30) of patients with globozoospermia. Furthermore, knockdown of the Kifc1 gene in mice increased the percentage of sperm with globozoospermic defects (26.5%). Decreased KIFC1 expression was mainly observed in the testes of patients with globozoospermia at the spermatid stage, which may be useful for counseling and management of such patients.

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Identification of a newDPY19L2mutation and a better definition ofDPY19L2deletion breakpoints leading to globozoospermia

Cited by 38 publications

References 27 publications

Comparison of sperm morphology and nuclear sperm quality in SPATA16‐ and DPY19L2‐ mutated globozoospermic patients

Comparison of sperm morphology and nuclear sperm quality in SPATA16‐ and DPY19L2‐ mutated globozoospermic patients

Genetic abnormalities leading to qualitative defects of sperm morphology or function

Decreased Expression of KIFC1 in Human Testes with Globozoospermic Defects

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