A reinvestigation of non-disjunction resulting in 47, XXY males of paternal origin

Thomas, N. Simon; Collins, Andrew; Hassold, Terry; Jacobs, Patricia A.

doi:10.1038/sj.ejhg.5200531

Cited by 55 publications

(43 citation statements)

References 18 publications

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“…The origin of maternally derived cases (47,X M X M Y) is also variable; approximately 48% are due to meiosis I errors, 29% to meiosis II errors, 7% to meiotic origins in which the specific stage is unknown, and 16% to postzygotic mitotic errors. 4 The relationship between parental age and these different cytogenetic origins of 47,XXY is complex. Consistent with autosomal trisomies, there is no obvious increase in the age of the father among paternally derived cases.…”

Section: Cytogenetic Origin and Molecular Pathogenesismentioning

confidence: 99%

“…Cases originating at maternal meiosis II appear to be maternal age-independent. 4 Although we still know little of the molecular basis of autosomal trisomies, studies indicate an association between altered genetic recombination and nondisjunction. 3 Recent studies of sex chromosome trisomies indicate that this relationship holds for 47,XXY as well.…”

Section: Cytogenetic Origin and Molecular Pathogenesismentioning

confidence: 99%

“…Approximately two-thirds of paternally derived cases are attributable to these so-called "achiasmate" meioses. 4 Failure to recombine is also important in the genesis of 47,X M X M Y cases. Thomas et al 5 estimated that approximately 25% of these cases involve maternal meioses in which the two X chromosomes fail to pair and/or recombine with each other.…”

Section: Cytogenetic Origin and Molecular Pathogenesismentioning

confidence: 99%

See 2 more Smart Citations

Klinefelter syndrome: Expanding the phenotype and identifying new research directions

Simpson

Cruz

Swerdloff

et al. 2003

Genetics in Medicine

177

160

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Section: Cytogenetic Origin and Molecular Pathogenesismentioning

confidence: 99%

Section: Cytogenetic Origin and Molecular Pathogenesismentioning

confidence: 99%

Section: Cytogenetic Origin and Molecular Pathogenesismentioning

confidence: 99%

See 1 more Smart Citation

Klinefelter syndrome: Expanding the phenotype and identifying new research directions

Simpson

Cruz

Swerdloff

et al. 2003

Genetics in Medicine

177

160

View full text Add to dashboard Cite

“…6 for proposed model on the SAC response). Unfortunately, in human males both X-Y segregation and SAC surveillance appear to be substantially less efficient, as indicated by observations that defective X-Y pairing often results in aneuploidies (Hassold et al, 1991;Thomas et al, 2000). There is substantial inter-individual variability: first, in the inherent propensity to X-Y recombination defects; and second, in the stringency with which meiocytes defective for sex chromosome recombination are eliminated (Ferguson et al, 2007).…”

Section: Mlh1mentioning

confidence: 99%

Reduced MAD2 levels dampen the apoptotic response to non-exchange sex chromosomes and lead to sperm aneuploidy

Faisal¹,

Kauppi²

2017

Journal of Cell Science

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In meiosis, non-exchange homologous chromosomes are at risk for mis-segregation and should be monitored by the spindle assembly checkpoint (SAC) to avoid formation of aneuploid gametes. Sex chromosome mis-segregation is particularly common and can lead to sterility or to aneuploid offspring (e.g. individuals with Turner or Klinefelter syndrome). Despite major implications for health and reproduction, modifiers of meiotic SAC robustness and the subsequent apoptotic response in male mammals remain obscure. Levels of SAC proteins, e.g. MAD2, are crucial for normal checkpoint function in many experimental systems, but surprisingly, apparently not in male meiosis, as indicated by the lack of chromosome segregation defects reported earlier in Mad2 +/− spermatocytes. To directly test whether MAD2 levels impact the meiotic response to missegregating chromosomes, we used Spo11β-only mb mice that are prone to non-exchange X-Y chromosomes. We show that reduced MAD2 levels attenuate the apoptotic response to mis-segregating sex chromosomes and allow the formation of aneuploid sperm. These findings demonstrate that SAC protein levels are crucial for the efficient elimination of aberrant spermatocytes.

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“…The well established risk factor for nondisjunction is advanced maternal age. There are contradicting reports regarding the influence of maternal age resulting in sex chromosomal aneuploidy (Warburton et al 1980;Ferguson-Smith andYates 1984, Gravholt et al 1996;Robinson and Jacobs 1999;Thomas et al 2000;Lowe et al 2001;Ranke and Saenger 2001;Lanfranco et al 2004). Even the evidences for paternal age as a risk factor for autosomal and sex chromosomal aneuploidy births remain ambiguous (de Michelena et al 1993;MacDonald et al 1994;Wyrobek et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Advanced Maternal Grandmother Age is a Risk Factor in Causing Sex Chromosomal Aneuploidy

Malini

Savitha

Krishnamurthy

et al. 2007

International Journal of Human Genetics

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Majority of the chromosomal abnormalities are incompatible with embryonic or fetal survival but trisomy 21 and sex chromosomal trisomies have a much higher viability surviving to term. In India, increased numbers of children with sex chromosomal aneuploidy are born to young mothers. Therefore, detailed analysis of the families with sex chromosomal aneuploidy is needed to find out the possible causative factors for nondisjunction. Twenty five families of suspected sex chromosomal aneuploidy children were investigated for cytogenetic analysis and pedigrees were constructed for these families. As controls 100 randomly selected families belonging to different religions were used. Of the 25 sex chromosomal aneuploidy cases studied, 16 were Turners with 45, XO chromosomes and 9 were Klinefelters with 47, XXY chromosomes. The number of sex chromosomal aneuploidy births was greater for the young mothers than the advanced age mothers. The logistic regression of case-control study of sex chromosomal aneuploidy children revealed that the odds ratio for the age of maternal grandmother was significant when all the four variables were used once at a time. However, the effect of age of mother and father was smaller than the effect of age of maternal grandmother. For every year of advancement of age of the maternal grandmother, the risk (odds) of births of sex chromosomal aneuploidy children increases by 36%. Therefore, the age of the maternal grandmother at the time of birth of mother is a risk factor for the occurrence of sex chromosomal aneuploidy.

show abstract

A reinvestigation of non-disjunction resulting in 47, XXY males of paternal origin

Cited by 55 publications

References 18 publications

Klinefelter syndrome: Expanding the phenotype and identifying new research directions

Klinefelter syndrome: Expanding the phenotype and identifying new research directions

Reduced MAD2 levels dampen the apoptotic response to non-exchange sex chromosomes and lead to sperm aneuploidy

Advanced Maternal Grandmother Age is a Risk Factor in Causing Sex Chromosomal Aneuploidy

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