RT Journal Article
SR Electronic
T1 Emerging patterns of cryptic chromosomal imbalance in patients with idiopathic mental retardation and multiple congenital anomalies: a new series of 140 patients and review of published reports
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 625
OP 633
DO 10.1136/jmg.2005.039453
VO 43
IS 8
A1 B Menten
A1 N Maas
A1 B Thienpont
A1 K Buysse
A1 J Vandesompele
A1 C Melotte
A1 T de Ravel
A1 S Van Vooren
A1 I Balikova
A1 L Backx
A1 S Janssens
A1 A De Paepe
A1 B De Moor
A1 Y Moreau
A1 P Marynen
A1 J-P Fryns
A1 G Mortier
A1 K Devriendt
A1 F Speleman
A1 J R Vermeesch
YR 2006
UL http://jmg.bmj.com/content/43/8/625.abstract
AB Background: 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. Objective: To report array CGH screening of a series of 140 patients (the largest published so far) with idiopathic MCA/MR but normal karyotype. Results: 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. Conclusions: 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.