Nonreciprocal and jumping translocations of 15q1→qter in Prader‐Willi syndrome

Rivera, Horacio; Zuffardi, Orsetta; Gargantini, L

doi:10.1002/ajmg.1320370304

Cited by 53 publications

(33 citation statements)

References 42 publications

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“…[31][32][33][34] JT in such cases are, however, also cytogenetically different compared to hematologic malignancies -they preferentially involve other donor chromosome regions and are not trisomic for the jumping region. [31][32][33][34][35] Altogether, the widespread temporally heterogeneous breakpoints of the donor chromosome and the subtelomeric breakpoints on the recipient chromosomes indicate a complex origin of JT: the multiple clones most likely arose more or less simultaneously, followed by clonal selection. In this context, it is noteworthy that a small clone with +3 preceded the unbalanced JT.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of jumping translocations reveals spatial and temporal breakpoint heterogeneity

et al. 1998

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Jumping translocations (JT) are characterized by the relocalization of the same part of a donor to several recipient chromosomes. Although JT occasionally are constitutional, most are associated with hematologic malignancies. In such cases, JT usually arise during disease progression and are associated with poor prognosis. Despite its clinical importance, this cytogenetic phenomenon has not been characterized at the molecular level. We have analyzed JT in a juvenile chronic myelomonocytic leukemia that subsequently transformed to an acute myeloid leukemia. Detailed fluorescence in situ hybridization (FISH) analyses showed that the cytogenetically identical donor breakpoint at 3q21 was highly heterogeneous. In fact, more than 10 distinct breakpoints, four of which mapped within YACs, were identified. Analyses of samples during disease progression showed that the breakpoint complexity decreased, indicating clonal selection. Hence, the 3q21 breakpoints displayed a spatial as well as a temporal heterogeneity, revealing that JT are highly unstable, showing great variation in the size of donor segment. The breaks at the recipient chromosomes were mapped within the subtelomeric regions. The general telomere length was not affected and an underlying replication error resulting in microsatellite instability was excluded. We conclude that the emergence of JT is unlikely to cause fusion genes or to affect the expression of genes located in the breakpoint regions. The identification of YACs spanning the breakpoints, ie, YACs 913c7, 937g5, 948c2 and 955g1, may facilitate the isolation of DNA sequences leading to a genetic instability associated with the origin of multiple translocations.

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Section: Discussionmentioning

confidence: 99%

Molecular characterization of jumping translocations reveals spatial and temporal breakpoint heterogeneity

et al. 1998

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“…Of the 346 subjects who performed FISH and/or microsatellite analysis, 68.8% had a del15, 30.05% had a UPD15 and 1.15% had a de novo translocation involving chromosome 15. Of the latter, two cases with a nonreciprocal translocation leading to 15pter-q13 monosomy have previously been described [Rivera et al, 1990]. The remaining two patients showed a 45,XY,der(9)t(9;15)(q34, q12),-15 and a 45,XX,der(15)t(15;20)(q12;q13.3), -15 karyotype, respectively.…”

Section: Population Datamentioning

confidence: 96%

The Italian National Survey for Prader–Willi syndrome: An epidemiologic study

Grugni

Crinò

Bosio

et al. 2008

American J of Med Genetics Pt A

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Twenty-five medical centers and the Prader-Willi Syndrome (PWS) Association collaborated on a study which attempted to identify all people with genetically confirmed diagnosis of PWS living in Italy. Investigators of the participating centers contacted PWS subjects and/or their family, filled in a specially developed form with the required data and forwarded this information by email. The study identified 425 subjects (209 males and 216 females, between the ages of 0.4-46.7). Two hundred thirty-eight patients had del15, 104 had UPD15, 4 demonstrated a translocation affecting chromosome 15 and 79 showed a positive methylation test. There were fewer subjects found over the age of 35, probably due to the low rate of identification of older PWS patients as well as the high mortality rate. There were a greater number of male children and adolescents with PWS whilst, amongst adults, there were more females. As expected, the majority of subjects with PWS were obese, especially in adult life. Nevertheless, it is noteworthy that 26% of patients aged between 6 and 17 were normal weight. A total of 212 subjects had received GH treatment, of which 141 were still receiving therapy, while the remaining 71 had stopped. In children and adolescents (233 cases), 89 subjects had never undergone GH therapy. Eighteen PWS patients had died in the past 20 years. Obesity-related cardiovascular and respiratory diseases were the cause of death, both during childhood and after 18 years of age. Three children died suddenly whilst undergoing GH therapy. Respiratory infection and cardiac illness were the causes of death in two cases. There was no definitive cause of death found in the third case. Overall, there was no increase in number of deaths during GH treatment, suggesting that GH administration in patients with PWS, as a group, does not increase the risk of death. ß

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“…PWS then occurs via either paternally derived deletions or maternally derived uniparental disomy, each the result of abnormal meiotic segregation. A review by Rivera et al [1990] reported that only 1 of 19 informative cases with a complex abnormality of chromosome 15 was inherited, so it appears that most structural abnormalities in PWS result from de novo event during gametogenesis. The recurrence risk is thus expected to be very low.…”

Section: Other Cytogenetic Abnormalitiesmentioning

confidence: 99%

Genetic counseling in Angelman syndrome: The challenges of multiple causes

Stalker

Williams

1998

Am. J. Med. Genet.

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The causal heterogeneity of Angelman syndrome (AS) makes providing information regarding recurrence risk both important and challenging, and may have a dramatic impact on reproductive decision-making for the nuclear and extended family. Most cases of AS result from typical large de novo deletions of 15q11-q13, and are expected to have a low (<1%) risk of recurrence. AS due to paternal uniparental disomy (UPD), which occurs in the absence of a parental translocation, is likewise expected to have a <1% risk of recurrence. Parental transmission of a structurally or functionally unbalanced chromosome complement can lead to 15q11-q13 deletions or to UPD and will result in case-specific recurrence risks. In instances where there is no identifiable large deletion or UPD, the risk for recurrence may be as high as 50% as the result of either a maternally inherited imprinting center (IC) mutation or a ubiquitin-protein ligase (UBE3A) gene mutation. Individuals with AS who have none of the above abnormalities comprise a significant proportion of cases, and some may be at a 50% recurrence risk. Misdiagnoses, as well, can be represented in this group. In light of the many conditions which are clinically similar to AS, it is essential to address the possibility of diagnostic uncertainty and potential misdiagnosis prior to the provision of genetic counseling. Summaries of the different causal classes of AS as an algorithm for determination of recurrence risks are presented.

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Nonreciprocal and jumping translocations of 15q1→qter in Prader‐Willi syndrome

Cited by 53 publications

References 42 publications

Molecular characterization of jumping translocations reveals spatial and temporal breakpoint heterogeneity

Molecular characterization of jumping translocations reveals spatial and temporal breakpoint heterogeneity

The Italian National Survey for Prader–Willi syndrome: An epidemiologic study

Genetic counseling in Angelman syndrome: The challenges of multiple causes

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