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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

Genetic diagnosis of aurora kinase C (AURKC) exons 3 and 6. Electropherogram showing part of AURKC exons 3 and 6 from a control subject (lane 2) and a patient with a homozygous c.144delC deletion of exon 3 (lane 3, column 2) and another patient with a homozygous p.Y248* mutation of exon 6 (lane 3, column 3). The reference nucleotide sequence and its translation are indicated at the top of the figure.
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Figure 2: Genetic diagnosis of aurora kinase C (AURKC) exons 3 and 6. Electropherogram showing part of AURKC exons 3 and 6 from a control subject (lane 2) and a patient with a homozygous c.144delC deletion of exon 3 (lane 3, column 2) and another patient with a homozygous p.Y248* mutation of exon 6 (lane 3, column 3). The reference nucleotide sequence and its translation are indicated at the top of the figure.

Mentions: The seven AURKC exons and their intron boundaries were amplified as previously described.4 All analyses were carried out with BigDye Terminator version 3.1 sequencing kits and an ABI PRISM 3130 genetic analyzer (Applied Biosystems, Foster City, CA, USA). The primers and protocols used were as described elsewhere.4 Example of the results obtained is shown in Figure 2.


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)

Genetic diagnosis of aurora kinase C (AURKC) exons 3 and 6. Electropherogram showing part of AURKC exons 3 and 6 from a control subject (lane 2) and a patient with a homozygous c.144delC deletion of exon 3 (lane 3, column 2) and another patient with a homozygous p.Y248* mutation of exon 6 (lane 3, column 3). The reference nucleotide sequence and its translation are indicated at the top of the figure.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Genetic diagnosis of aurora kinase C (AURKC) exons 3 and 6. Electropherogram showing part of AURKC exons 3 and 6 from a control subject (lane 2) and a patient with a homozygous c.144delC deletion of exon 3 (lane 3, column 2) and another patient with a homozygous p.Y248* mutation of exon 6 (lane 3, column 3). The reference nucleotide sequence and its translation are indicated at the top of the figure.
Mentions: The seven AURKC exons and their intron boundaries were amplified as previously described.4 All analyses were carried out with BigDye Terminator version 3.1 sequencing kits and an ABI PRISM 3130 genetic analyzer (Applied Biosystems, Foster City, CA, USA). The primers and protocols used were as described elsewhere.4 Example of the results obtained is shown in Figure 2.

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