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Malgorzata J M Nowaczyk - One of the best experts on this subject based on the ideXlab platform.
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prader willi syndrome and tay sachs disease in association with mixed maternal uniparental isoDisomy and heteroDisomy 15 in a girl who also had isochromosome xq
American Journal of Medical Genetics Part A, 2015Co-Authors: Susan Zeesman, Elizabeth Mccready, Bekim Sadikovic, Malgorzata J M NowaczykAbstract:Malsegregation of chromosomes during reproduction can result in uniparental Disomy when associated with trisomy rescue, monosomy rescue or gamete complementation. Pathogenicity stemming from uniparental Disomy in liveborns results from imprinting disorders or autozygosity for autosomal recessive disorders. We report on a girl with Prader–Willi syndrome and Tay–Sachs disease resulting from maternal uniparental Disomy of chromosome 15. The child also had an isochromosome Xq. To further characterize the etiology of the aberrant chromosome 15 and the isochromosome Xq, SNP loci from both chromosomes were assessed in the proband and parents, and genome-wide DNA methylation analysis was performed. SNP and DNA methylation analysis confirmed maternal uniparental heteroDisomy around the Prader–Willi locus, while the region around the HEXA locus showed maternal uniparental isoDisomy. This result is consistent with trisomy rescue of a maternal meiosis l error in a chromosome 15 with two meiotic recombinations. SNP analysis of the X chromosomes is consistent with a maternal origin for the isochromosome. © 2014 Wiley Periodicals, Inc.
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prader willi syndrome and tay sachs disease in association with mixed maternal uniparental isoDisomy and heteroDisomy 15 in a girl who also had isochromosome xq
American Journal of Medical Genetics Part A, 2015Co-Authors: Susan Zeesman, Elizabeth Mccready, Bekim Sadikovic, Malgorzata J M NowaczykAbstract:Malsegregation of chromosomes during reproduction can result in uniparental Disomy when associated with trisomy rescue, monosomy rescue or gamete complementation. Pathogenicity stemming from uniparental Disomy in liveborns results from imprinting disorders or autozygosity for autosomal recessive disorders. We report on a girl with Prader-Willi syndrome and Tay-Sachs disease resulting from maternal uniparental Disomy of chromosome 15. The child also had an isochromosome Xq. To further characterize the etiology of the aberrant chromosome 15 and the isochromosome Xq, SNP loci from both chromosomes were assessed in the proband and parents, and genome-wide DNA methylation analysis was performed. SNP and DNA methylation analysis confirmed maternal uniparental heteroDisomy around the Prader-Willi locus, while the region around the HEXA locus showed maternal uniparental isoDisomy. This result is consistent with trisomy rescue of a maternal meiosis l error in a chromosome 15 with two meiotic recombinations. SNP analysis of the X chromosomes is consistent with a maternal origin for the isochromosome.
Dieter Kotzot - One of the best experts on this subject based on the ideXlab platform.
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complex and segmental uniparental Disomy updated
Journal of Medical Genetics, 2008Co-Authors: Dieter KotzotAbstract:Objective: To review all cases with segmental and/or complex uniparental Disomy (UPD) and to discuss the impact of these cases on Medical Genetics. Design: Searching for published reports in Pubmed and in the abstract books of the annual meetings of the American Society of Human Genetics and the European Society of Human Genetics up to March 2008. Results: In total, 26 cases with segmental UPD and a normal karyotype, 38 cases with UPD of a whole chromosome and a simple reciprocal or non-homologous Robertsonisn translocation, four cases each with two isochromosomes and UPD of the short arm isochromosme and opposite UPD of the long arm isochromosome, three cases with UPD and an isochromosome of the short arm and the long arm of a metacentric or a submetacentric chromosome, one case with maternal UPD and an isochromosome 8 associated with a homozygous deletion (8)(p23.3pter), 42 cases with UPD and an isochromosome of the long arm of an acrocentric chromosome, 33 cases with UPD and a supernumerary marker or ring chromosome, 17 cases with UPD of a whole or parts of a chromosome and a complex karyotype, 13 cases with most likely mosaicism for genome-wide paternal UPD, and 3 cases with most likely mosaicism for genome-wide maternal UPD were found. Conclusion: This update shows that particularly the number of reported cases with segmental UPD or UPD associated with a marker chromosome clearly increased within the last years, and that the investigation of both parents in cases with homozygosity of an autosomal recessively inherited mutation in some cases might help improving genetic counselling coming to a reduced recurrence risk in the case of UPD. Moreover, cases with segmental or complex UPD show that meiosis and early postzygotic mitoses seem to be more complex events than previously thought. For the formation of all kinds of segmental or complex UPD or genome-wide UPD mosaicism always a fortunate cooccurrence of meiotic or mitotic recombination, abnormal segregation, and subsequent correction are necessary. No case of recurrence has been reported until now. Therefore, in subsequent pregnancies invasive prenatal diagnosis is not necessarily indicated.
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uniparental Disomy 7 in silver russell syndrome and primordial growth retardation
Human Molecular Genetics, 1995Co-Authors: Silke Schmitt, Helena G Ilyina, Dieter Kotzot, Iosif W Lurie, Wendy P. Robinson, Fosco Bernasconi, K MéhesAbstract:: Maternal uniparental Disomy for the entire chromosome 7 has so far been reported in three patients with intrauterine and postnatal growth retardation. Two were detected because they were homozygous for a cystic fibrosis mutation for which only the mother was heterozygous, and one because he was homozygous for a rare COL1A2 mutation. We investigated 35 patients with either the Silver-Russell syndrome or primordial growth retardation and their parents with PCR markers to search for uniparental Disomy 7. Four of 35 patients were found to have maternal Disomy, including three with isoDisomy and one with heteroDisomy. The data confirm the hypothetical localization of a maternally imprinted gene (or more than one such gene) on chromosome 7. It is suggested to search for UPD 7 in families with an offspring with sporadic Silver-Russell syndrome or primordial growth retardation.
Albert Schinzel - One of the best experts on this subject based on the ideXlab platform.
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pericentric inversion of chromosome 18 in parents leading to a phenotypically normal child with segmental uniparental Disomy 18
European Journal of Human Genetics, 2011Co-Authors: Ariana Kariminejad, Azadeh Moshtagh, Mohammad Hassan Kariminejad, Roxana Kariminejad, Maryam Zanganeh, Michal J. Okoniewski, Albert Schinzel, Stefan Neuenschwander, Alessandra BaumerAbstract:In this study, we report a familial inversion of chromosome 18, inv(18)(p11.31q21.33), in both members of a consanguineous couple. Their first child had inherited one balanced pericentric inversion along with a recombinant chromosome 18 resulting in dup(18q)/del(18p), and had mild dysmorphic features in the absence of mental and developmental retardation. The second child had received two recombinant chromosomes 18, from the mother a derivative chromosome 18 with dup(18p)/del(18q) and from the father a derivative chromosome 18 with dup(18q)/del(18p). The aberration was prenatally detected; however, as the two opposite aneuploidies were thought to compensate each other, the family decided to carry on with the pregnancy, knowing that uniparental Disomy for the segments outside the inversion could have an adverse influence on the development of the child. Uniparental Disomy was confirmed by SNP arrays. The child, who has been followed up until the age of 20 months, is healthy and normal. It seems to be the first reported case with two opposite recombinant chromosomes that compensate each other and lead to segmental uniparental Disomy for two segments on the chromosome, one maternal and the other paternal.
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maternal uniparental Disomy 14 as a cause of intrauterine growth retardation and early onset of puberty
The Journal of Pediatrics, 1999Co-Authors: Siv Fokstuen, Claudia Ginsburg, M Zachmann, Albert SchinzelAbstract:Uniparental Disomy for particular chromosomes is increasingly recognized as a cause of abnormal phenotypes in humans either as a result of imprinted genes or, in the case of isoDisomy, homozygosity of mutated recessive alleles. We report on the occurrence of maternal uniparental Disomy for chromosome 14 (matUPD 14) in a 25-year-old woman with a normal karyotype, normal intelligence but low birth weight, short stature, small hands, and early onset of puberty. Comparison of her phenotype with those of 15 previously described liveborn patients with matUPD14 gives further evidence for an imprinted gene region on chromosome 14 and highlights the necessity to consider this cause in children with intrauterine growth retardation and early onset of puberty caused by acceleration of skeletal maturation.
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molecular studies of chromosomal mosaicism relative frequency of chromosome gain or loss and possible role of cell selection
American Journal of Human Genetics, 1995Co-Authors: Wendy P. Robinson, F Bernasconi, Franz Binkert, Isabel Lordasanchez, Edmond A Werder, Albert SchinzelAbstract:Studies of uniparental Disomy and origin of nonmosaic trisomies indicate that both gain and loss of a chromosome can occur after fertilization. It is therefore of interest to determine both the relative frequency with which gain or loss can contribute to chromosomal mosaicism and whether these frequencies are influenced by selective factors. Thirty-two mosaic cases were examined with molecular markers, to try to determine which was the primary and which was the secondary cell line: 16 cases of Disomy/trisomy mosaicism (5 trisomy 8, 2 trisomy 13, 1 trisomy 18, 4 trisomy 21, and 4 involving the X chromosome), 14 cases of 45,X/46,XX, and 2 cases of 45,X/47,XXX. Of the 14 cases of mosaic 45,X/46,XX, chromosome loss from a normal disomic fertilization predominated, supporting the hypothesis that 45,X might be compatible with survival only when the 45,X cell line arises relatively late in development. Most cases of Disomy/trisomy mosaicism involving chromosomes 13, 18, 21, and X were also frequently associated with somatic loss of one (or more) chromosome, in these cases from a trisomic fertilization. By contrast, four of the five trisomy 8 cases were consistent with a somatic gain of a chromosome 8 during development from a normal zygote. It is possible that survival of trisomy 8 is also much more likely when the aneuploid cell line arises relatively late in development.
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uniparental Disomy explains the occurrence of the angelman or prader willi syndrome in patients with an additional small inv dup 15 chromosome
Journal of Medical Genetics, 1993Co-Authors: Wendy P. Robinson, J Wagstaff, F Bernasconi, Carlo Baccichetti, L Artifoni, Emilio Franzoni, L Suslak, Lingyu Shih, H Aviv, Albert SchinzelAbstract:A patient with Angelman syndrome and a 46,XY/47,XY,+inv dup(15)(pter-->q11: q11-->pter) karyotype and a patient with Prader-Willi syndrome and a 46,XY/47,XY,+inv dup(15)(pter-->q12: q12-->pter) karyotype were investigated with molecular markers along chromosome 15. Paternal uniparental isoDisomy was found for all informative markers in the first case which indicates that this, rather than the presence of the extra chromosome, is the cause of the Angelman syndrome phenotype. Similarly, the PWS patient showed maternal uniparental distomy with absence of PWS region material on the inv dup(15) chromosome. If (1) marker chromosomes are an occasional by product of 'rescuing' a trisomic fertilisation, or (2) if duplication of the normal homologue in a zygote which has inherited a marker in place of the normal corresponding chromosome 'rescues' an aneuploid fertilisation, or (3) if the presence or formation of a marker chromosome increases the probability of non-disjunction, then uniparental Disomy might be found occasionally in other subjects with de novo marker chromosomes.
Melissa J Perry - One of the best experts on this subject based on the ideXlab platform.
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pesticide interactions and risks of sperm chromosomal abnormalities
International Journal of Hygiene and Environmental Health, 2019Co-Authors: Zaida I Figueroa, Dana B. Barr, Heather A Young, John D Meeker, Sunni L Mumford, George M Gray, Melissa J PerryAbstract:Disentangling the separate and synergistic effects of chemicals poses methodological challenges for accurate exposure assessment and for investigating epidemiologically how chemicals affect reproduction. We investigated combined exposures to ubiquitous contemporary use pesticides, specifically organophosphates (OP) and pyrethroids (PYR), and their association with germ cell abnormalities among adult men. Fluorescence in situ hybridization was used to determine Disomy in sperm nuclei and urine was analyzed for concentrations of PYR metabolites (3-phenoxybenzoic acid; 3PBA) and OP dialkyl phosphate (DAP) metabolites. Incidence rate ratios using Poisson models were estimated for each Disomy type by exposure quartile of DAP metabolites and 3PBA, controlling for confounders. The shape of the associations between PYRs, OPs and Disomy were frequently nonmonotonic. There were consistent interactions between OP and PYR metabolite concentrations and the risk for sperm abnormalities. Taking both chemicals into account simultaneously resulted in quantitatively different associations than what was reported previously for OPs and PYRs separately, demonstrating the importance of modeling multiple concentrations simultaneously. Methods investigating interactions using Poisson models are needed to better quantify chemical interactions and their effects on count-based health outcomes, the importance of which was shown here for germ cell abnormalities.
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human sperm sex chromosome Disomy and sperm dna damage assessed by the neutral comet assay
Human Reproduction, 2014Co-Authors: Megan E Mcauliffe, Paige L Williams, Susan A Korrick, Ramace Dadd, Francesco Marchetti, Sheena E Martenies, Melissa J PerryAbstract:STUDY QUESTION Is there an association between human sperm sex chromosome Disomy and sperm DNA damage?
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environmental exposure to pyrethroids and sperm sex chromosome Disomy a cross sectional study
Environmental Health, 2013Co-Authors: Heather A Young, Sheena E Martenies, John D Meeker, Zaida I Figueroa, Melissa J PerryAbstract:Background The role of environmental pesticide exposures, such as pyrethroids, and their relationship to sperm abnormalities are not well understood. This study investigated whether environmental exposure to pyrethroids was associated with altered frequency of sperm sex chromosome Disomy in adult men.
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environmental exposure to pyrethroids and sperm sex chromosome Disomy a cross sectional study
Environmental Health, 2013Co-Authors: Heather A Young, Sheena E Martenies, John D Meeker, Zaida I Figueroa, Melissa J PerryAbstract:The role of environmental pesticide exposures, such as pyrethroids, and their relationship to sperm abnormalities are not well understood. This study investigated whether environmental exposure to pyrethroids was associated with altered frequency of sperm sex chromosome Disomy in adult men. A sample of 75 subjects recruited through a Massachusetts infertility clinic provided urine and semen samples. Individual exposures were measured as urinary concentrations of three pyrethroid metabolites ((3-phenoxybenzoic acid (3PBA), cis- and trans- 3-(2,2-Dichlorovinyl)-1-methylcyclopropane-1,2-dicarboxylic acid (CDCCA and TDCCA)). Multiprobe fluorescence in situ hybridization for chromosomes X, Y, and 18 was used to determine XX, YY, XY, 1818, and total sex chromosome Disomy in sperm nuclei. Poisson regression analysis was used to examine the association between aneuploidy rates and pyrethroid metabolites while adjusting for covariates. Between 25-56% of the sample were above the limit of detection (LOD) for the pyrethroid metabolites. All sex chromosome disomies were increased by 7-30% when comparing men with CDCCA and TDCCA levels above the LOD to those below the LOD. For 3PBA, compared to those below the LOD, those above the LOD had YY18 Disomy rates 1.28 times higher (95% CI: 1.15, 1.42) whereas a reduced rate was seen for XY18 and total Disomy (IRR = 0.82; 95% CI: 0.77, 0.87; IRR = 0.93; 95% CI: 0.87-0.97), and no association was seen for XX18 and 1818. Our findings suggest that urinary concentrations of CDCCA and TDCCA above the LOD were associated with increased rates of aneuploidy. However the findings for 3BPA were not consistent. This is the first study to examine these relationships, and replication of our findings is needed before the association between pyrethroid metabolites and aneuploidy can be fully defined.
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the association between sperm sex chromosome Disomy and semen concentration motility and morphology
Human Reproduction, 2012Co-Authors: Megan E Mcauliffe, Paige L Williams, Susan A Korrick, Ramace Dadd, Melissa J PerryAbstract:STUDY QUESTION Is there an association between sex chromosome Disomy and semen concentration, motility and morphology?
Wendy P. Robinson - One of the best experts on this subject based on the ideXlab platform.
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uniparental Disomy 7 in silver russell syndrome and primordial growth retardation
Human Molecular Genetics, 1995Co-Authors: Silke Schmitt, Helena G Ilyina, Dieter Kotzot, Iosif W Lurie, Wendy P. Robinson, Fosco Bernasconi, K MéhesAbstract:: Maternal uniparental Disomy for the entire chromosome 7 has so far been reported in three patients with intrauterine and postnatal growth retardation. Two were detected because they were homozygous for a cystic fibrosis mutation for which only the mother was heterozygous, and one because he was homozygous for a rare COL1A2 mutation. We investigated 35 patients with either the Silver-Russell syndrome or primordial growth retardation and their parents with PCR markers to search for uniparental Disomy 7. Four of 35 patients were found to have maternal Disomy, including three with isoDisomy and one with heteroDisomy. The data confirm the hypothetical localization of a maternally imprinted gene (or more than one such gene) on chromosome 7. It is suggested to search for UPD 7 in families with an offspring with sporadic Silver-Russell syndrome or primordial growth retardation.
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molecular studies of chromosomal mosaicism relative frequency of chromosome gain or loss and possible role of cell selection
American Journal of Human Genetics, 1995Co-Authors: Wendy P. Robinson, F Bernasconi, Franz Binkert, Isabel Lordasanchez, Edmond A Werder, Albert SchinzelAbstract:Studies of uniparental Disomy and origin of nonmosaic trisomies indicate that both gain and loss of a chromosome can occur after fertilization. It is therefore of interest to determine both the relative frequency with which gain or loss can contribute to chromosomal mosaicism and whether these frequencies are influenced by selective factors. Thirty-two mosaic cases were examined with molecular markers, to try to determine which was the primary and which was the secondary cell line: 16 cases of Disomy/trisomy mosaicism (5 trisomy 8, 2 trisomy 13, 1 trisomy 18, 4 trisomy 21, and 4 involving the X chromosome), 14 cases of 45,X/46,XX, and 2 cases of 45,X/47,XXX. Of the 14 cases of mosaic 45,X/46,XX, chromosome loss from a normal disomic fertilization predominated, supporting the hypothesis that 45,X might be compatible with survival only when the 45,X cell line arises relatively late in development. Most cases of Disomy/trisomy mosaicism involving chromosomes 13, 18, 21, and X were also frequently associated with somatic loss of one (or more) chromosome, in these cases from a trisomic fertilization. By contrast, four of the five trisomy 8 cases were consistent with a somatic gain of a chromosome 8 during development from a normal zygote. It is possible that survival of trisomy 8 is also much more likely when the aneuploid cell line arises relatively late in development.
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uniparental Disomy explains the occurrence of the angelman or prader willi syndrome in patients with an additional small inv dup 15 chromosome
Journal of Medical Genetics, 1993Co-Authors: Wendy P. Robinson, J Wagstaff, F Bernasconi, Carlo Baccichetti, L Artifoni, Emilio Franzoni, L Suslak, Lingyu Shih, H Aviv, Albert SchinzelAbstract:A patient with Angelman syndrome and a 46,XY/47,XY,+inv dup(15)(pter-->q11: q11-->pter) karyotype and a patient with Prader-Willi syndrome and a 46,XY/47,XY,+inv dup(15)(pter-->q12: q12-->pter) karyotype were investigated with molecular markers along chromosome 15. Paternal uniparental isoDisomy was found for all informative markers in the first case which indicates that this, rather than the presence of the extra chromosome, is the cause of the Angelman syndrome phenotype. Similarly, the PWS patient showed maternal uniparental distomy with absence of PWS region material on the inv dup(15) chromosome. If (1) marker chromosomes are an occasional by product of 'rescuing' a trisomic fertilisation, or (2) if duplication of the normal homologue in a zygote which has inherited a marker in place of the normal corresponding chromosome 'rescues' an aneuploid fertilisation, or (3) if the presence or formation of a marker chromosome increases the probability of non-disjunction, then uniparental Disomy might be found occasionally in other subjects with de novo marker chromosomes.
