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Mutations of the aurora kinase C gene causing macrozoospermia are the most frequent genetic cause of male infertility in Algerian men.

Ounis L, Zoghmar A, Coutton C, Rouabah L, Hachemi M, Martinez D, Martinez G, Bellil I, Khelifi D, Arnoult C, Fauré J, Benbouhedja S, Rouabah A, Ray PF - Asian J. Androl. (2015 Jan-Feb)

Bottom Line: Eleven men with macrozoospermia had a homozygous AURKC mutation (79%), corresponding to 2.7% of all patients with abnormal spermograms.By comparison, we would expect 1.6% of the patients in this cohort to have Klinefelter syndrome and 0.23% to have Y-microdeletion.Furthermore, we estimate that AURKC and DPY19L2 molecular defects are 10 and 5 times more frequent, respectively, than Y-microdeletions.

View Article: PubMed Central - PubMed

Affiliation: Université Grenoble Alpes; Equipe Génétique Epigénétique et Thérapies de l'Infertilité, CNRS, AGIM; Laboratoire de Biochimie et Génétique Moléculaire, CHU Grenoble, Grenoble, France, .

ABSTRACT
Klinefelter syndrome and Y-chromosomal microdeletion analyses were once the only two genetic tests offered to infertile men. Analyses of aurora kinase C (AURKC) and DPY19L2 are now recommended for patients presenting macrozoospermia and globozoospermia, respectively, two rare forms of teratozoospermia particularly frequent among North African men. We carried out genetic analyses on Algerian patients, to evaluate the prevalence of these syndromes in this population and to compare it with the expected frequency of Klinefelter syndrome and Y-microdeletions. We carried out a retrospective study on 599 consecutive patients consulting for couple infertility at the assisted reproduction unit of the Ibn Rochd Clinique, Constantine, Algeria. Abnormal sperm parameters were observed in 404 men. Fourteen and seven men had typical macrozoospermia and globozoospermia profiles, respectively. Molecular diagnosis was carried out for these patients, for the AURKC and DPY19L2 genes. Eleven men with macrozoospermia had a homozygous AURKC mutation (79%), corresponding to 2.7% of all patients with abnormal spermograms. All the men with globozoospermia studied (n = 5), corresponding to 1.2% of all infertile men, presented a homozygous DPY19L2 deletion. By comparison, we would expect 1.6% of the patients in this cohort to have Klinefelter syndrome and 0.23% to have Y-microdeletion. Our findings thus indicate that AURKC mutations are more frequent than Klinefelter syndrome and constitute the leading genetic cause of infertility in North African men. Furthermore, we estimate that AURKC and DPY19L2 molecular defects are 10 and 5 times more frequent, respectively, than Y-microdeletions.

No MeSH data available.


Related in: MedlinePlus

Multiplex ligation-dependent probe amplification (MLPA) analysis of DPY19L2 exons 1, 17 and 22. The probe set contained three control probes for normalization purposes (c1, c2, c3) and three specific DPY19L2 probes (X1, X17 and X22) corresponding to exons 1, 17 and 22 of DPY19L2, respectively. Lane 1: MLPA profile of a normal DNA sample (control). Lane 2: MLPA profile of a patient with a homozygous deletion, showing a total absence of DPY19L2 exon signals. Lane 3: MLPA profile of a patient with a heterozygous deletion, showing a halving of the intensity of the DPY19L2 signals.
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Figure 3: Multiplex ligation-dependent probe amplification (MLPA) analysis of DPY19L2 exons 1, 17 and 22. The probe set contained three control probes for normalization purposes (c1, c2, c3) and three specific DPY19L2 probes (X1, X17 and X22) corresponding to exons 1, 17 and 22 of DPY19L2, respectively. Lane 1: MLPA profile of a normal DNA sample (control). Lane 2: MLPA profile of a patient with a homozygous deletion, showing a total absence of DPY19L2 exon signals. Lane 3: MLPA profile of a patient with a heterozygous deletion, showing a halving of the intensity of the DPY19L2 signals.

Mentions: For this study, three synthetic multiplex ligation-dependent probe amplification (MLPA) probes specific to exons 1, 17 and 22 of DPY19L2 were used, as previously described.12 Given the high level of sequence similarity between DPY19L2 and other DPY19L paralogs and pseudogenes, MLPA probes were designed to match specific DPY19L2 single-nucleotide mismatches at the ligation site.16 We also included three MLPA control probes specific to the OCRL1 gene, as control probes for the determination of copy number. Information about the sequences and ligation sites of these control probes can be obtained from the study by Coutton et al.17 A comparison of the heights of the signals obtained for the control and target probes provides information about the number of copies of the target sequence present in the sampled DNA (Figure 3).


Mutations of the aurora kinase C gene causing macrozoospermia are the most frequent genetic cause of male infertility in Algerian men.

Ounis L, Zoghmar A, Coutton C, Rouabah L, Hachemi M, Martinez D, Martinez G, Bellil I, Khelifi D, Arnoult C, Fauré J, Benbouhedja S, Rouabah A, Ray PF - Asian J. Androl. (2015 Jan-Feb)

Multiplex ligation-dependent probe amplification (MLPA) analysis of DPY19L2 exons 1, 17 and 22. The probe set contained three control probes for normalization purposes (c1, c2, c3) and three specific DPY19L2 probes (X1, X17 and X22) corresponding to exons 1, 17 and 22 of DPY19L2, respectively. Lane 1: MLPA profile of a normal DNA sample (control). Lane 2: MLPA profile of a patient with a homozygous deletion, showing a total absence of DPY19L2 exon signals. Lane 3: MLPA profile of a patient with a heterozygous deletion, showing a halving of the intensity of the DPY19L2 signals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4291881&req=5

Figure 3: Multiplex ligation-dependent probe amplification (MLPA) analysis of DPY19L2 exons 1, 17 and 22. The probe set contained three control probes for normalization purposes (c1, c2, c3) and three specific DPY19L2 probes (X1, X17 and X22) corresponding to exons 1, 17 and 22 of DPY19L2, respectively. Lane 1: MLPA profile of a normal DNA sample (control). Lane 2: MLPA profile of a patient with a homozygous deletion, showing a total absence of DPY19L2 exon signals. Lane 3: MLPA profile of a patient with a heterozygous deletion, showing a halving of the intensity of the DPY19L2 signals.
Mentions: For this study, three synthetic multiplex ligation-dependent probe amplification (MLPA) probes specific to exons 1, 17 and 22 of DPY19L2 were used, as previously described.12 Given the high level of sequence similarity between DPY19L2 and other DPY19L paralogs and pseudogenes, MLPA probes were designed to match specific DPY19L2 single-nucleotide mismatches at the ligation site.16 We also included three MLPA control probes specific to the OCRL1 gene, as control probes for the determination of copy number. Information about the sequences and ligation sites of these control probes can be obtained from the study by Coutton et al.17 A comparison of the heights of the signals obtained for the control and target probes provides information about the number of copies of the target sequence present in the sampled DNA (Figure 3).

Bottom Line: Eleven men with macrozoospermia had a homozygous AURKC mutation (79%), corresponding to 2.7% of all patients with abnormal spermograms.By comparison, we would expect 1.6% of the patients in this cohort to have Klinefelter syndrome and 0.23% to have Y-microdeletion.Furthermore, we estimate that AURKC and DPY19L2 molecular defects are 10 and 5 times more frequent, respectively, than Y-microdeletions.

View Article: PubMed Central - PubMed

Affiliation: Université Grenoble Alpes; Equipe Génétique Epigénétique et Thérapies de l'Infertilité, CNRS, AGIM; Laboratoire de Biochimie et Génétique Moléculaire, CHU Grenoble, Grenoble, France, .

ABSTRACT
Klinefelter syndrome and Y-chromosomal microdeletion analyses were once the only two genetic tests offered to infertile men. Analyses of aurora kinase C (AURKC) and DPY19L2 are now recommended for patients presenting macrozoospermia and globozoospermia, respectively, two rare forms of teratozoospermia particularly frequent among North African men. We carried out genetic analyses on Algerian patients, to evaluate the prevalence of these syndromes in this population and to compare it with the expected frequency of Klinefelter syndrome and Y-microdeletions. We carried out a retrospective study on 599 consecutive patients consulting for couple infertility at the assisted reproduction unit of the Ibn Rochd Clinique, Constantine, Algeria. Abnormal sperm parameters were observed in 404 men. Fourteen and seven men had typical macrozoospermia and globozoospermia profiles, respectively. Molecular diagnosis was carried out for these patients, for the AURKC and DPY19L2 genes. Eleven men with macrozoospermia had a homozygous AURKC mutation (79%), corresponding to 2.7% of all patients with abnormal spermograms. All the men with globozoospermia studied (n = 5), corresponding to 1.2% of all infertile men, presented a homozygous DPY19L2 deletion. By comparison, we would expect 1.6% of the patients in this cohort to have Klinefelter syndrome and 0.23% to have Y-microdeletion. Our findings thus indicate that AURKC mutations are more frequent than Klinefelter syndrome and constitute the leading genetic cause of infertility in North African men. Furthermore, we estimate that AURKC and DPY19L2 molecular defects are 10 and 5 times more frequent, respectively, than Y-microdeletions.

No MeSH data available.


Related in: MedlinePlus