The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Lisa G Shaffer - One of the best experts on this subject based on the ideXlab platform.
-
mosaicism in a patient with down syndrome reveals post fertilization formation of a robertsonian translocation and Isochromosome
American Journal of Medical Genetics Part A, 2003Co-Authors: Ruma Bandyopadhyay, Sue Ann Berend, Christopher Mccaskill, Lisa G Shaffer, Cami Knoxdu Bois, Yaolin Zhou, Emilia K BijlsmaAbstract:It has been estimated that a few hundred children are born each year in the United States with translocation Down syndrome. About 5% of the cases with Down syndrome carry a Robertsonian translocation involving chromosome 21. The case described here is a patient with Down syndrome who showed mosaicism for two cell lines. Each cell line contains a different, de novo acrocentric rearrangement. We constructed somatic cell hybrids from the patient's cells and determined the parental origins of the rearrangements by molecular and fluorescence in situ hybridization (FISH) analyses. The analysis showed that the rob(14q21q) formed between a paternally inherited chromosome 21 and a maternally inherited chromosome 14, indicating that this rearrangement formed post-zygotically. Further molecular analysis also determined that the rea(21q21q) is an Isochromosome of paternal origin. The cell line containing the Isochromosome is unbalanced, resulting in trisomy 21. Because the same paternal chromosome 21 was involved in both the Isochromosome and the Robertsonian translocation, we speculate that an unstable chromosome 21 was stabilized either through formation of a rob(14q21q) or through formation of an Isochromosome. The mechanism proposed for the formation of the rob(14q21q) in this case is different from that for most de novo rob(14q21q), but similar to a previously reported mosaic case of Down syndrome. © 2002 Wiley-Liss, Inc.
-
investigation of two cases of paternal disomy 13 suggests timing of Isochromosome formation and mechanisms leading to uniparental disomy
American Journal of Medical Genetics, 1999Co-Authors: Sue Ann Berend, Gerald L Feldman, Christopher Mccaskill, Paula Czarnecki, Daniel L Van Dyke, Lisa G ShafferAbstract:Uniparental disomy (UPD) is the abnormal inheritance of two copies of a chromosome from the same parent. Possible mechanisms for UPD include trisomy rescue, monosomy rescue, gametic complementation, and somatic recombination. Most of these mechanisms can involve rearranged chromosomes, particularly Isochromosomes and Robertsonian translocations. Both maternal and paternal UPD have been reported for most of the acrocentric chromosomes. However, only UPD for chromosomes 14 and 15 show an apparent imprinting effect. Herein, we present two cases of paternal UPD 13 involving Isochromosomes. Both cases were referred for UPD studies due to the formation of a de novo rea(13q13q). Case 2 was complicated by the segregation of a familial rob(13q14q) of maternal origin. Both propositi were phenotypically normal at the time of examination. Polymorphic marker analysis in Case 1 showed the distribution of alleles of markers along chromosome 13 to be complete isodisomy, consistent with an Isochromosome. This rearrangement could have occurred either meiotically, without recombination, or mitotically. A likely mechanism for UPD in this case is monosomy rescue, through postzygotic formation of the Isochromosome. In Case 2 the distribution of proximal alleles indicated an Isochromosome, but recombination was evident. Thus, this Isochromosome must have formed prior to or during meiosis I. A likely mechanism for UPD in this case is gametic complementation, since the mother carries a rob(13q14q) and is at risk of producing aneuploid gametes. However, trisomy rescue of a trisomy 13 conceptus cannot be completely excluded. Given that both cases were phenotypically normal, these data further support that paternal UPD 13 does not have an adverse phenotypic outcome and, thus, does not show an apparent imprinting effect. Am. J. Med. Genet. 82:275–281, 1999. © 1999 Wiley-Liss, Inc.
-
molecular characterization of de novo secondary trisomy 13
American Journal of Human Genetics, 1994Co-Authors: Lisa G Shaffer, Christopher Mccaskill, K H A Choo, D M Cutillo, A E Donnenfeld, Lester Weiss, D L Van DykeAbstract:Unbalanced Robertsonian translocations are a significant cause of mental retardation and fetal wastage. The majority of homologous rearrangements of chromosome 21 in Down syndrome have been shown to be Isochromosomes. Aside from chromosome 21, very little is known about other acrocentric homologous rearrangements. In this study, four cases of de novo secondary trisomy 13 are presented. FISH using alpha-satellite sequences, rDNA, and a pTRI-6 satellite I sequence specific to the short arm of chromosome 13 showed all four rearrangements to be dicentric an apparently devoid of ribosomal genes. Three of four rearrangements retained the pTRI-6 satellite I sequence. Case 1 was the exception, showing a deletion of this sequence in the rearrangement, although both parental chromosomes 13 had strong positive hybridization signals. Eleven microsatellite markers from chromosome 13 were also used to characterize the rearrangements. Of the four possible outcomes, one maternal Robertsonian translocation, two paternal Isochromosomes, and one maternal Isochromosomes were observed. A double recombination was observed in the maternally derived rob(13q13q). No recombination events were detected in any Isochromosome. The parental origins and molecular chromosomal structure of these cases are compared with previous studies of de novo acrocentric rearrangements. 20 refs., 3 figs., 2 tabs.
-
A molecular genetic approach to the identification of Isochromosomes of chromosome 21.
Human Genetics, 1991Co-Authors: Lisa G Shaffer, Colleen Jackson-cook, Joanne M. Meyer, Judith A. Brown, J. Edward SpenceAbstract:The largest class of de novo chromosomal rearrangements in Down syndrome are rea(21q21q). Classically, these rearrangements have been termed Robertsonian translocations, implying an attachment of two different chromosome 21 homologues. Additionally, a Robertsonian translocation between two chromosomes 21 cannot be distinguished from an Isochromosome composed of genetically identical arms by cytogenetic analyses. Therefore, we have used molecular techniques to differentiate between true Robertsonian translocations and Isochromosomes. Samples were obtained from 12 probands, ascertained for de novo rearrangements between homologous chromosomes 21 [11 rea(21q21q) and 1 rea (21;21)(q22;q22)], their parents (n = 24) and available siblings (n = 7). The parental origins of the de novo rearrangements were assigned using molecular and cytogenetic analyses. Although not statistically significant, there was a two-fold increase in the number of paternally derived de novo rearrangements (n = 8) as compared with maternally derived rearrangements (n = 4). To distinguish between rob(21q21q) and i(21q), we used restriction fragment length polymorphisms (RFLPs) spanning the length of chromosome 21. Using all informative and partially informative RFLPs, we used the method of maximum likelihood to assign the most likely rearrangement definition (i or rob) and parental origin in each family. The maximum likelihood estimates indicated that all rearrangements tested (n = 8) were Isochromosomes. C-banding revealed two centromeres in three cases indicating that a U-type exchange occurred between sister chromatids in these rearrangements. Our results suggest that the majority of de novo rea(21q21q) are Isochromosomes derived from a single parental chromosome 21.
M Lecornu - One of the best experts on this subject based on the ideXlab platform.
-
turner s syndrome with x Isochromosome and hashimoto s thyroiditis
Clinical Endocrinology, 1994Co-Authors: M De Kerdanet, J Lucas, F Lemee, M LecornuAbstract:OBJECTIVE: The higher frequency of Hashimoto's thyroiditis in Turner's syndrome compared with the general population is well known. We have attempted to establish clearly the more frequent association of thyroiditis with the X-Isochromosome, since previous reports of this aspect have included only small numbers of patients. DESIGN: Retrospective study of patients with Turner's syndrome investigated within the past 12 years. PATIENTS: Sixty-seven cases of Turner's syndrome were reviewed. MEASUREMENTS: Peripheral blood leucocyte karyotype and screening for thyroid disturbances on the basis of clinical examination and laboratory evaluation (anti-thyroglobulin and anti-microsomal antibodies, basal TSH levels and TSH levels after TRH stimulation) were made for each patient. RESULTS: A diagnosis of thyroiditis, based on the association of positive antibody titres, elevated TSH and an abnormal thyroid gland on clinical examination, was established in 20.9% (14/67) of cases. A significantly higher frequency of thyroiditis was found among the patients presenting with an X-Isochromosome (57.3%, 9/16), compared to patients with other karyotypes (9.8%, 5/51) (P = 0.0001). CONCLUSIONS: Our results, obtained by investigation of a larger number of patients with an X-Isochromosome karyotype than in previous reports, confirm conclusively that patients with X-Isochromosome Turner's syndrome have an increased risk of developing thyroiditis.
-
Turner's syndrome with X‐Isochromosome and Hashimoto's thyroiditis
Clinical Endocrinology, 1994Co-Authors: M De Kerdanet, J Lucas, F Lemee, M LecornuAbstract:OBJECTIVE: The higher frequency of Hashimoto's thyroiditis in Turner's syndrome compared with the general population is well known. We have attempted to establish clearly the more frequent association of thyroiditis with the X-Isochromosome, since previous reports of this aspect have included only small numbers of patients. DESIGN: Retrospective study of patients with Turner's syndrome investigated within the past 12 years. PATIENTS: Sixty-seven cases of Turner's syndrome were reviewed. MEASUREMENTS: Peripheral blood leucocyte karyotype and screening for thyroid disturbances on the basis of clinical examination and laboratory evaluation (anti-thyroglobulin and anti-microsomal antibodies, basal TSH levels and TSH levels after TRH stimulation) were made for each patient. RESULTS: A diagnosis of thyroiditis, based on the association of positive antibody titres, elevated TSH and an abnormal thyroid gland on clinical examination, was established in 20.9% (14/67) of cases. A significantly higher frequency of thyroiditis was found among the patients presenting with an X-Isochromosome (57.3%, 9/16), compared to patients with other karyotypes (9.8%, 5/51) (P = 0.0001). CONCLUSIONS: Our results, obtained by investigation of a larger number of patients with an X-Isochromosome karyotype than in previous reports, confirm conclusively that patients with X-Isochromosome Turner's syndrome have an increased risk of developing thyroiditis.
Philippe Vago - One of the best experts on this subject based on the ideXlab platform.
-
prenatal detection of mosaic Isochromosome 20q a fourth report with abnormal phenotype
Prenatal Diagnosis, 2005Co-Authors: Carole Goumy, A M Beaufrere, Christine Francannet, Andrei Tchirkov, Laurichesse H Delmas, F Geissler, D Lemery, P Dechelotte, Philippe VagoAbstract:We described a new case of mosaic Isochromosome 20q revealed by amniocentesis. The propositus presented with craniofacial dysmorphism, clubfeet, and vertebral abnormalities. A 46,XX,i(20)(q10)[14]/46,XX[1] karyotype was confirmed by FISH on cultured cells. The pregnancy was terminated. From review of literature, fetus with mosaic Isochromosome 20q identified on amniocentesis are most likely to be phenotypically and cytogenetically normal after birth. So we performed CGH and array-CGH to exclude another possible imbalance. We discuss here the possible relation between this chromosomal abnormality and the abnormal phenotype. Copyright © 2005 John Wiley & Sons, Ltd.
Wendy P. Robinson - One of the best experts on this subject based on the ideXlab platform.
-
pregnancy and postnatal outcome of mosaic Isochromosome 20q
Prenatal Diagnosis, 2007Co-Authors: Wendy P. Robinson, Barbara Mcgillivray, Jan M FriedmanAbstract:Prenatally diagnosed mosaicism for Isochromosome 20q is generally reported in association with a normal outcome at birth and is rarely confirmed postnatally. However, the origin of these abnormal cells is unclear and there are few reports of long-term outcomes. We present an additional case of prenatally detected Isochromosome 20q, with normal outcome up to age 3.6 years. The abnormal cells, while present at high levels in the amniotic fluid, could not be confirmed in placenta or fetal blood. Nonetheless, based on a review of the literature, the level of Isochromosome 20q cells found is associated with risk of abnormal outcome, suggesting a possible effect in some cases. Copyright © 2006 John Wiley & Sons, Ltd.
-
Grandmaternal origin of an Isochromosome 18p present in two maternal half‐sisters
American Journal of Medical Genetics, 2001Co-Authors: Jane Boyle, Wendy P. Robinson, Karan Sangha, Fred J Dill, Siuli YongAbstract:The syndrome of tetrasomy 18p has been well documented in the literature. This is typically a result of a supernumerary Isochromosome 18p, that has arisen during maternal meiosis II. This report presents clinical and molecular findings in two maternal half sisters with an Isochromosome 18p. The Isochromosome is inferred to have arisen during meiosis in the maternal grandmother and to have undergone mitotic and meiotic recombination in the mother of JJ and AT. The abnormal cell line may be restricted to the gonad in the mother as only normal 46,XX cells were detected by cytogenetic analysis of her blood or fibroblasts and physical examination revealed only normal findings. Thus, the Isochromosome, although present at fertilization, must have been lost from the majority of embryonic precursor cells. This case raises important genetic counseling issues concerning recurrence risks.
-
grandmaternal origin of an Isochromosome 18p present in two maternal half sisters
American Journal of Medical Genetics, 2001Co-Authors: Jane Boyle, Wendy P. Robinson, Karan Sangha, Fred J Dill, Siuli YongAbstract:The syndrome of tetrasomy 18p has been well documented in the literature. This is typically a result of a supernumerary Isochromosome 18p, that has arisen during maternal meiosis II. This report presents clinical and molecular findings in two maternal half sisters with an Isochromosome 18p. The Isochromosome is inferred to have arisen during meiosis in the maternal grandmother and to have undergone mitotic and meiotic recombination in the mother of JJ and AT. The abnormal cell line may be restricted to the gonad in the mother as only normal 46,XX cells were detected by cytogenetic analysis of her blood or fibroblasts and physical examination revealed only normal findings. Thus, the Isochromosome, although present at fertilization, must have been lost from the majority of embryonic precursor cells. This case raises important genetic counseling issues concerning recurrence risks.
-
A somatic origin of homologous Robertsonian translocations and Isochromosomes.
American Journal of Human Genetics, 1994Co-Authors: Wendy P. Robinson, F. Bernasconi, Seher Basaran, Memnune Yuksel-apak, G. Neri, F. Serville, P. Balicek, R. Haluza, L. M. S. Farah, Guven LuleciAbstract:One t(14q 14q), three t(15q 15q), two t(21q21q), and two t(22q22q) nonmosaic, apparently balanced, de novo Robertsonian translocation cases were investigated with polymorphic markers to establish the origin of the translocated chromosomes. Four cases had results indicative of an Isochromosome: one t(14q14q) case with mild mental retardation and maternal uniparental disomy (UPD) for chromosome 14, one t(15q15q) case with the Prader-Willi syndrome and UPD(15), a phenotypically normal carrier of t(22q22q) with maternal UPD(22), and a phenotypically normal t(21q21q) case of paternal UPD(21). All UPD cases showed complete homozygosity throughout the involved chromosome, which is supportive of a postmeiotic origin. In the remaining four cases, maternal and paternal inheritance of the involved chromosome was found, which unambiguously implies a somatic origin. One t(15q15q) female had a child with a ring chromosome 15, which was also of probable postmeiotic origin as recombination between grandparental haplotypes had occurred prior to ring formation. UPD might be expected to result from de novo Robertsonian translocations of meiotic origin; however, all de novo homologous translocation cases, so far reported, with UPD of chromosomes 14, 15, 21, or 22 have been Isochromosomes. These data provide the first direct evidence that nonmosaic Robertsonian translocations, as well as Isochromosomes,more » are commonly the result of a mitotic exchange. 75 refs., 1 fig., 4 tabs.« less
Wolfgang Kern - One of the best experts on this subject based on the ideXlab platform.
-
the landscape of myeloid neoplasms with Isochromosome 17q discloses a specific mutation profile and is characterized by an accumulation of prognostically adverse molecular markers
Leukemia, 2016Co-Authors: Manja Meggendorfer, Wolfgang Kern, C Haferlach, Melanie Zenger, Katja Macijewski, T HaferlachAbstract:The landscape of myeloid neoplasms with Isochromosome 17q discloses a specific mutation profile and is characterized by an accumulation of prognostically adverse molecular markers
-
setbp1 mutations occur in 9 of mds mpn and in 4 of mpn cases and are strongly associated with atypical cml monosomy 7 Isochromosome i 17 q10 asxl1 and cbl mutations
Leukemia, 2013Co-Authors: Manja Meggendorfer, Wolfgang Kern, C Haferlach, T Haferlach, U Bacher, Tamara Alpermann, Carlo Gambacortipasserini, S SchnittgerAbstract:SETBP1 mutations occur in 9% of MDS/MPN and in 4% of MPN cases and are strongly associated with atypical CML, monosomy 7, Isochromosome i(17)(q10), ASXL1 and CBL mutations
-
gain of an Isochromosome 5p a new recurrent chromosome abnormality in acute monoblastic leukemia
Cancer Genetics and Cytogenetics, 2001Co-Authors: Claudia Schoch, Sabina Bursch, Wolfgang Kern, Susanne Schnittger, Wolfgang Hiddemann, Torsten HaferlachAbstract:Abstract In acute myeloid leukemia (AML) close associations are known between cytomorphology and cytogenetics such as in AML M3/M3v showing a t(15;17) and in AML M4eo associated with inv(16)/t(16;16). In AML M5 a heterogenous cytogenetic pattern is observed. We describe the gain of an Isochromosome of the short arm of chromosome 5 together with the gain of chromosome 8 as the sole abnormalities in two cases of acute monoblastic leukemia. In a third case of acute monoblastic leukemia we also observed the gain of an Isochromosome 5p together with trisomy 8. This patient showed in addition an unbalanced translocation between the long arm of chromosome 1 and the short arm of chromosome 14 leading to a trisomy 1q. So far only two cases of AML with i(5)(p10) have been published. In no other hematological malignancy has an Isochromosome 5p been reported up to now. As an Isochromosome 5p can be misinterpreted as a deletion 5q, which occurs frequently in AML, fluorescence in situ hybridization with loci specific probes is a helpful method to detect this rare abnormality.
-
short communication gain of an Isochromosome 5p a new recurrent chromosome abnormality in acute monoblastic leukemia
2001Co-Authors: Claudia Schoch, Sabina Bursch, Wolfgang Kern, Susanne Schnittger, Wolfgang Hiddemann, Torsten HaferlachAbstract:In acute myeloid leukemia (AML) close associations are known between cytomorphology and cy- togenetics such as in AML M3/M3v showing a t(15;17) and in AML M4eo associated with inv(16)/ t(16;16). In AML M5 a heterogenous cytogenetic pattern is observed. We describe the gain of an Isochromosome of the short arm of chromosome 5 together with the gain of chromosome 8 as the sole abnormalities in two cases of acute monoblastic leukemia. In a third case of acute monoblastic leukemia we also observed the gain of an Isochromosome 5p together with trisomy 8. This patient showed in addition an unbalanced translocation between the long arm of chromosome 1 and the short arm of chromosome 14 leading to a trisomy 1q. So far only two cases of AML with i(5)(p10) have been published. In no other hematological malignancy has an Isochromosome 5p been re- ported up to now. As an Isochromosome 5p can be misinterpreted as a deletion 5q, which occurs frequently in AML, fluorescence in situ hybridization with loci specific probes is a helpful method to detect this rare abnormality. © 2001 Elsevier Science Inc. All rights reserved.
