Comparative genomic hybridisation in mentally retarded patients with dysmorphic features and a normal karyotype

Abstract

Segmental aneusomy for small chromosomal regions has been shown to be a common cause of mental retardation and multiple congenital anomalies. A screening method for such chromosome aberrations that are not detected using standard cytogenetic techniques is needed. Recent studies have focused on detection of subtle terminal chromosome aberrations using subtelomeric probes. This approach however excludes significant regions of the genome where submicroscopic rearrangements are also liable to occur. The aim of the present study was to evaluate the efficiency of comparative genomic hybridisation (CGH) for screening of submicroscopic chromosomal rearrangements. CGH was performed in a cohort of 17 patients (14 families) with mental retardation, dysmorphic features and a normal karyotype. Five subtle unbalanced rearrangements were identified in 7 patients. Subsequent FISH studies confirmed these results. Although no interstitial submicroscopic rearrangement was detected in this small series, the study emphasises the value of CGH as a screening approach to detect subtle chromosome rearrangements in mentally retarded patients with dysmorphic features and a normal karyotype.

Telomeres: a diagnosis at the end of the chromosomes

“…A der(2)t(2;7)(q73;q36) was detected in a severely cognitively retarded 3 year old boy with facial dysmorphism (prominent forehead, downward slanting palpebral fissures, arched eyebrows, long eyelashes, small mouth with short philtrum and thin upper lip), a few café au lait spots, pectus carinatum, and talipes equinovarus. 30 Mildly mentally retarded patients with 2qter deletions and an inconsistent clinical phenotype have been reported [31][32][33] and Figure 1 Clinical photographs of various patients with subtelomere deletions.…”

“…80 Joly et al 33 reported a 2 month old, severely mentally retarded infant with low birth weight, hypotonia, severe myopia, and a perineal angioma and der(10)t(10;12)(p12;p12) diagnosed by comparative genomic hybridisation. In retrospect, the derivative chromosome 10 was detectable in the original karyotype.…”

“…Joly et al 33 reported a severely retarded 1 month old girl with a deletion 7pter and partial trisomy for 16qter with dolichocephaly, hypertelorism, micrognathia, vertebral anomalies (not specified), anteriorly placed anus, and brain stem dysfunction. Eleven cases with microscopically visible deletion 7p22.1-pter have been reported, some with facial anomalies (notably broad, flat nasal bridge, low set, malformed ears), digital anomalies, cardiac defects, and hypoplastic genitals.…”

The end of the beginning of chromosome ends†

“…The results of these studies contribute to a suddenly sizable body of data. Including the three papers in this issue, I have identi®ed 14 studies that include 1,718 subjects [Flint et al, 1995;Vorsanova et al, 1998;Knight et al, 1999;Lamb et al, 1999;Slavotinek et al, 1999;Joly et al, 2001;Borgione et al, 2001;Colleaux et al, 2001;Rossi et al, 2001;Anderlid et al, 2002;Baker et al, 2002;Clarkson et al, 2002;Riegel et al, 2001;Rosenberg et al, 2001]. (Table I).…”

Detection of an interstitial deletion of 2q21‐22 by high resolution comparative genomic hybridization in a child with multiple congenital anomalies and an apparent balanced translocation

“…Kirchhof et al [2001] reported six abnormalities in 25 apparently balanced de novo translocations associated with phenotypic changes. Joly et al [2001] detected seven imbalances in 17 patients with mental retardation, dysmorphic features, and normal karyotypes, and Ness et al [2002] found a deletion or duplication in 5 of 50 patients with apparently normal karyotypes and various degrees of delayed psychomotor development with or without Fig. 3.…”