Phenotypic variation within European carriers of the Y-chromosomal gr/gr deletion is independent of Y-chromosomal background

Krausz, Csilla; Giachini, Claudia; Xue, Yali; O'Bryan, Moira K; Gromoll, Jörg; Meyts, Ewa Rajpert‐De; Oliva, Rafael; Aknin‐Seifer, Isabelle; Erdei, E.; Jørgensen, Niklas Rye; Simoni, Manuela; Ballescà, Josep Lluís; Levy, Roei; Balercia, Giancarlo; Piomboni, Paola; Nieschlag, Eberhard; Forti, Gianni; McLachlan, Robert I; Tyler‐Smith, Chris

doi:10.1136/jmg.2008.059915

Cited by 67 publications

(91 citation statements)

References 29 publications

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“…In the present study, we observed that not all men with AZFc subdeletions had the expected deletion of DAZ and CDY1 gene copies. As reported previously [36], there were several men who had DAZ and/or CDY1 gene copies intact despite having gr/gr, b1/b3 or b2/b3 deletion. To determine the impact of the DAZ and CDY1 copy deletions, we classified the men with AZFc subdeletions (gr/gr, b1/b3 and b2/b3) based on the DAZ and CDY1 gene copies deleted.…”

Section: Discussionsupporting

confidence: 70%

“…Thus based on this analysis we could argue that the sY1291/sY1191 based screening strategy might be associated with false detections. Indeed based on a similar strategy, Krausz et al, reported a false deletion rate of 5.3 % [36]; in the present study it was calculated as 19.4 % (14/72). This was not due to PCR failures as a biplex reaction was optimized where the housekeeping SRY was always co-amplified.…”

Section: Discussionsupporting

confidence: 54%

“…It has been observed that not all men harbouring AZFc subdeletions (based on sY1291/sY1191 based screening) have loss of both DAZ and CDY1 gene copies [34,36]. Corroborating these observations further, copy number variations of DAZ and CDY1 genes were found to be associated with reduction in total motile sperm count in men harbouring AZFc subdeletions [37].…”

Section: Introductionmentioning

confidence: 94%

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Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions

Sen

Ambulkar

Hinduja

et al. 2015

J Assist Reprod Genet

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Purpose The purpose of this study was to determine the association of AZFc subdeletions (gr/gr, b1/b3 and b2/b3) and deletion of DAZ and CDY1 gene copies with male infertility Methods Three hundred twelve controls, 172 azoospermic and 343 oligozoospermic subjects were subjected to AZFc subdeletion typing by STS PCR. Deletion of DAZ and CDY1 gene copies was done using sequence family variant analysis. Sperm concentration and motility were compared between men with and without AZFc subdeletions. Effect of the AZFc subdeletions on ICSI outcome was evaluated. Results Amongst the three AZFc subdeletions, the frequency of gr/gr was higher in oligozoospermic (10.5 %) and azoospermic (11.6 %) men as compared to controls (5.1 %). In men with AZFc subdeltions, loss of two DAZ and one CDY1 gene copy made them highly susceptible to azoospermia and severe oligozoospermia with OR of 29.7 and 26, respectively. These subdeletions had no effect on ICSI outcome, albeit there were an increased number of poor quality embryos in AZFc subdeleted group. Conclusion AZFc subdeletions are a major risk factor for male infertility in the Indian population. In the subjects with AZFc subdeletions, the deletion of DAZ and CDY1 gene copies increases its susceptibility to azoospermia or severe oligozoospermia. Since these deletions can be vertically transmitted to the future male offspring by ICSI, it will be essential to counsel the couples for the transmission of the genetic defect in the male offspring born after assisted reproduction and the risk of perpetuating infertility in future generation.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionsupporting

confidence: 54%

Section: Introductionmentioning

confidence: 94%

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Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions

Sen

Ambulkar

Hinduja

et al. 2015

J Assist Reprod Genet

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“…38,39 The majority of gr/gr deletion carriers belonged, as expected, to the P,Q,R branches in both patients and controls, supporting that the phenotypic variability of gr/gr deletion is independent of Y-chromosomal background in Europeans. 40 Interestingly, we found b2/b3 deletion only in the patient cohort (4/296; 1.3%) and only one carrier belonged to hgr N and thus had the constitutive b2/b3 deletion. The remaining three b2/b3 deletion carriers belonged to hrgs C,F,G,H,I, which is a frequent Y hgr in Moroccan population for which b2/b3 deletion has been recently reported in association with male infertility.…”

Section: -124mentioning

confidence: 62%

Clinical relevance of Y-linked CNV screening in male infertility: new insights based on the 8-year experience of a diagnostic genetic laboratory

et al. 2013

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AZF microdeletion screening is routinely performed in the diagnostic work-up for male infertility; however, some issues remain debated. In this study, we provide insights into the sperm concentration cutoff value for routine testing, the predictive value of AZFc deletion for testicular sperm retrieval and the Y-background contribution to the interpopulation variability of deletion frequencies. In the Spanish population, partial AZFc rearrangements have been poorly explored and no data exist on partial duplications. In our study, 27/806 (3.3%) patients carried complete AZF deletions. All were azoo/cryptozoospermic, except for one whose sperm concentration was 2 Â 10 6 /ml. In AZFc-deleted men, we observed a lower sperm recovery rate upon conventional TESE (9.1%) compared with the literature (60-80% with microTESE). Haplogroup E was the most represented among non-Spanish and hgr P among Spanish AZF deletion carriers. The analysis of AZFc partial rearrangements included 330 idiopathic infertile patients and 385 controls of Spanish origin. Gr/gr deletion, but not AZFc partial duplications, was significantly associated with spermatogenic impairment. Our data integrated with the literature suggest that: (1) routine AZF microdeletion testing could eventually include only men with r2 Â 10 6 /ml; (2) classical TESE is associated with low sperm recovery rate in azoospermic AZFc-deleted men, and therefore microTESE should be preferred; (3) Y background could partially explain the differences in deletion frequencies among populations. Finally, our data on gr/gr deletion further support the inclusion of this genetic test in the work-up of infertile men, whereas partial AZFc duplications do not represent a risk for spermatogenic failure in the Spanish population.

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“…59 However, given a 5% false deletion rate detected in a recent multicenter study, 63 deletions should be confirmed by gene dosage analysis. 63,64 There are mainly two reasons for gr/gr deletion testing in infertile men: i) the deletion contributes to the etiopathogenesis of impaired sperm production since it is able to influence the spermatogenic potential of the carrier; ii) the couple should be aware that the deletion (i.e. a genetic risk factor for impaired sperm production) will be obligatorily transmitted to their male offspring and the deletion may become complete AZFc deletion (i.e.…”

Section: Gr/gr Deletionmentioning

confidence: 99%

Male infertility: Pathogenesis and clinical diagnosis

Krausz¹

2011

Best Practice & Research Clinical Endocrinology & Metab

420

315

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Phenotypic variation within European carriers of the Y-chromosomal gr/gr deletion is independent of Y-chromosomal background

Abstract: The phenotypic variation of gr/gr carriers in men of European origin is largely independent of the Y-chromosomal background.

Cited by 67 publications

References 29 publications

Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions

Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions

Clinical relevance of Y-linked CNV screening in male infertility: new insights based on the 8-year experience of a diagnostic genetic laboratory

Male infertility: Pathogenesis and clinical diagnosis

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