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S Cingoz,
A M Bisgaard,
I Bache,
T Bryndorf,
M Kirchoff,
W Petersen,
H-H Ropers, N Maas,
G Van Buggenhout,
N Tommerup,
Z Tümer
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ABSTRACT: We report a familial cryptic reciprocal translocation between 4q35 and 10p15 leading to deletion of the terminal long arm of chromosome 4 and duplication of the terminal short arm of chromosome 10 in two family members who both have immunological disturbances and a similar facial appearance. The precise location and extent of the deletion and duplication was determined by fluorescence in situ hybridization (FISH). Furthermore, we investigated the deletion breakpoint of a previously reported patient with 4q34.3-qter deletion [Van Buggenhout et al. (2004); Am J Med Genet Part A 131A:186-189].
American Journal of Medical Genetics Part A 11/2006; 140(20):2231-5. · 2.39 Impact Factor
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B Menten, N Maas,
B Thienpont,
K Buysse,
J Vandesompele,
C Melotte,
T de Ravel,
S Van Vooren,
I Balikova,
L Backx,
S Janssens,
A De Paepe,
B De Moor,
Y Moreau,
P Marynen,
J-P Fryns,
G Mortier,
K Devriendt,
F Speleman,
J R Vermeesch
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ABSTRACT: Chromosomal abnormalities are a major cause of mental retardation and multiple congenital anomalies (MCA/MR). Screening for these chromosomal imbalances has mainly been done by standard karyotyping. Previous array CGH studies on selected patients with chromosomal phenotypes and normal karyotypes suggested an incidence of 10-15% of previously unnoticed de novo chromosomal imbalances.
To report array CGH screening of a series of 140 patients (the largest published so far) with idiopathic MCA/MR but normal karyotype.
Submicroscopic chromosomal imbalances were detected in 28 of the 140 patients (20%) and included 18 deletions, seven duplications, and three unbalanced translocations. Seventeen of 24 imbalances were confirmed de novo and 19 were assumed to be causal. Excluding subtelomeric imbalances, our study identified 11 clinically relevant interstitial submicroscopic imbalances (8%). Taking this and previously reported studies into consideration, array CGH screening with a resolution of at least 1 Mb has been undertaken on 432 patients with MCA/MR. Most imbalances are non-recurrent and spread across the genome. In at least 8.8% of these patients (38 of 432) de novo intrachromosomal alterations have been identified.
Array CGH should be considered an essential aspect of the genetic analysis of patients with MCA/MR. In addition, in the present study three patients were mosaic for a structural chromosome rearrangement. One of these patients had monosomy 7 in as few as 8% of the cells, showing that array CGH allows detection of low grade mosaicisims.
Journal of Medical Genetics 09/2006; 43(8):625-33. · 6.36 Impact Factor
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Genetic counseling (Geneva, Switzerland) 02/2006; 17(4):477-9. · 0.50 Impact Factor
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ABSTRACT: Molecular karyotyping has revealed that microdeletions/duplications in the human genome are a major cause of multiple congenital anomalies associated with mental retardation (MCA/MR). The identification of a de novo chromosomal imbalance in a patient with MCA/MR is usually considered causal for the phenotype while a chromosomal imbalance inherited from a phenotypically normal parent is considered as a benign variation and not related to the disorder. Around 40% of imbalances in patients with MCA/MR in this series is inherited from a healthy parent and the majority of these appear to be (extremely) rare variants. As some of these contain known disease-causing genes and have also been found to be de novo in MCA/MR patients, this challenges the general view that such familial variants are innocent and of no major phenotypic consequence. Rather, we argue, that human genomes can be tolerant of genomic copy number variations depending on the genetic and environmental background and that different mechanisms play a role in determining whether these chromosomal imbalances manifest themselves.
Cytogenetic and Genome Research 02/2006; 115(3-4):225-30. · 1.53 Impact Factor
