Isochromosome 15q of maternal origin in two Prader‐Willi syndrome patients previously diagnosed erroneously as cytogenetic deletions

Saitoh, Shinji; Mutirangura, Apiwat; Kuwano, Atsutoshi; Ledbetter, David H.; Niikawa, Norio

doi:10.1002/ajmg.1320500114

Cited by 13 publications

(9 citation statements)

References 24 publications

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“…Mitchell et al [1996] suggested as a possible explanation a bias of ascertaintment due to a milder phenotype in female UPD patients or difference in survival of early trisomy 15 conseptuses. However, there is no male predominance among Prader-Willi patients with UPD caused by isochromosome 15: five males [Hawkey and Smithies, 1976;Fraccaro et al, 1977;Saitoh et al, 1994;Bettio et al, 1996] and 10 females [Emberger et al, 1977;Flieschnick et al, 1979;Bauch et al, 1980;Berry et al, 1982;Ledbetter et al, 1982;Tylki et al, 1982;Winsor and Welch, 1983;Schmutz et al, 1984;Robinson et al, 1994;Saitoh et al, 1994] have been reported. The authors also suggested a possible difference in the probability of trisomic zygote rescue depending on the sex of the fetus [Mitchell et al, 1996].…”

Section: Parent-sex-specific Chromosome Lossmentioning

confidence: 96%

Sex-specific chromosome instability in early human development

Kovaleva

2005

Am. J. Med. Genet.

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The predominance of females segregating chromosome aberrations to their offspring has been explained mostly by selection disadvantage of unbalanced products of spermatogenesis. However, analysis of data from the literature supports the idea that somatic cells of early female embryos are similar to female germ cells in that they are prone to malsegregation. The goal of this study was to compare the sex ratio (male to female ratio) of carriers of presumably mitotic-occurring chromosome abnormalities to identify any sex biases. In examining the literature, we found a female prevalence in cases of mosaicism associated with uniparental disomy (UPD) (26 male individuals/conceptions and 45 female individuals/conceptions, sex ratio is 0.58, significantly different from 1.06 in newborn population, P = 0.0292). This predominance was highest at gestational age <16 week (8 male and 22 female conceptuses, sex ratio is 0.36, significantly different from expected figure of 1.28, P = 0.0025), which diminished at later stages of fetal development indicating potential correction of trisomies predominantly in females. There is a threefold prevalence of 46,XX/45,X mosaics over 46,XY/45,X mosaics in prenatally diagnosed cases, which also suggests a gender-specific postzygotic chromosome loss. The male prevalence in Prader-Willi syndrome with maternal UPD of chromosome 15 also can be explained by sex-specific trisomy correction, with predominant loss of a maternal chromosome causing biparental inheritance and therefore, complete correction of trisomy in females (without UPD). Finally, there is a female predominance in carriers of chromosome rearrangement with pericentromere break (mosaicism for Robertsonian translocation/isochromosome, centric fission, nonacrocentric isochromosome, and whole arm rearrangement), in both prenatal (21 males and 36 females, sex ratio is 0.58, P < 0.0184) and postnatal ill-defined cases (14 males and 35 females, sex ratio is 0.40, P = 0.001). Thus, the findings presented in this paper suggest that, in addition to reduction in male fertility, and to probable selection against abnormal cell line(s), there are two mechanisms that contribute to female preponderance among carriers of mosaicism: sex-specific chromosome loss and sex-specific centromere instability. The data obtained suggest that females may have gonadal mosaicism for aneuploidies and structural rearrangements more often than males. This may lead to the maternal origin bias in offspring with trisomies or structural rearrangements.

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Section: Parent-sex-specific Chromosome Lossmentioning

confidence: 96%

Sex-specific chromosome instability in early human development

Kovaleva

2005

Am. J. Med. Genet.

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“…Isochromosomes are mirror image chromosomes that are comprised of two copies of either a short arm or a long arm. Isochromosomes are observed most often for the X chromosome (48,139) and the acrocentric chromosomes (111,115,117,118). These rearrangements are distinguished from translocations in that isochromosomes are comprised of genetically identical arms, derived from a single chromosome (115,117).…”

Section: Intrachromosomal Rearrangementsmentioning

confidence: 98%

Molecular Mechanisms for Constitutional Chromosomal Rearrangements in Humans

2000

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Cytogenetic imbalance in the newborn is a frequent cause of mental retardation and birth defects. Although aneuploidy accounts for the majority of imbalance, structural aberrations contribute to a significant fraction of recognized chromosomal anomalies. This review describes the major classes of constitutional, structural cytogenetic abnormalities and recent studies that explore the molecular mechanisms that bring about their de novo occurrence. Genomic features flanking the sites of recombination may result in susceptibility to chromosomal rearrangement. One such substrate for recombination is low-copy region-specific repeats. The identification of genome architectural features conferring susceptibility to rearrangements has been accomplished using methods that enable investigation of regions of the genome that are too small to be visualized by traditional cytogenetics and too large to be resolved by conventional gel electrophoresis. These investigations resulted in the identification of previously unrecognized structural cytogenetic anomalies, which are associated with genetic syndromes and allowed for the molecular basis of some chromosomal rearrangements to be delineated.

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“…The less tests required, the more cost effective the diagnosis becomes. Retesting after an incomplete diagnosis is costly (51). As a baseline for comparison (52), in our genetic service in Sydney, Australia, the cost of a cytogenetic karyotype is $A365.00; a CMA is $A365.00; FISH test is $A175.00; methylation test is $A300.00 and MS-MLPA is $A300.00.…”

Section: Costmentioning

confidence: 99%

The dilemma of diagnostic testing for Prader-Willi syndrome

Smith

Hung

2017

Transl. Pediatr.

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Although Prader-Willi syndrome (PWS) is a well-described clinical dysmorphic syndrome, DNA testing is required for a definitive diagnosis. A definitive diagnosis can be made in approximately 99% of cases using DNA testing; there are a number of DNA tests that can be used for this purpose, although there is no set standard algorithm of testing. The dilemma arises because of the complex genetic mechanisms at the basis of PWS, which need to be elucidated. To establish the molecular mechanism with a complete work up, involves at least 2 tests. Here we discuss the commonly used tests currently available and suggest a costeffective approach to diagnostic testing.

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Isochromosome 15q of maternal origin in two Prader‐Willi syndrome patients previously diagnosed erroneously as cytogenetic deletions

Cited by 13 publications

References 24 publications

Sex-specific chromosome instability in early human development

Sex-specific chromosome instability in early human development

Molecular Mechanisms for Constitutional Chromosomal Rearrangements in Humans

The dilemma of diagnostic testing for Prader-Willi syndrome

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