The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation

Abstract

A major challenge for human genetics is to identify new causes of mental retardation, which, although present in about 3% of individuals, is unexplained in more than half of all cases. We have developed a strategy to screen for the abnormal inheritance of subtelomeric DNA polymorphisms in individuals with mental retardation and have detected three abnormalities in 99 patients with normal routine karyotypes. Pulsed-field gel electrophoresis and reverse chromosome painting showed that one case arose from an interstitial or terminal deletion and two from the de novo inheritance of derivative translocation chromosomes. At least 6% of unexplained mental retardation is accounted for by these relatively small chromosomal abnormalities, which will be an important resource in the characterization of the genetic basis of neurodevelopment.

FISH mapping of the sex-reversal region on human chromosome 9p in two XY females and in primates

“…The subtelomeres are proving to be a highly dynamic region of the human genome that play an important role in human chromosome pathology 22,23 and during chromosome evolution. 24 In order to study the chromosomal phylogeny of the sex-reversal region on human 9p, the 14 YACs listed in Figure 3 as well as PAC 8 were hybridised on chromosomes of chimpanzee (Pan troglodytes, PTR), gorilla (Gorilla gorilla, GGO), orangutan (Pongo pygmaeus, PPY), gibbon (Hylobates syndactylus, HSY), silvered leaf monkey (Presbytis cristata, P.cr.…”

Diagnostic investigations in individuals with mental retardation: a systematic literature review of their usefulness

“…One example is the publication by Flint and co-workers in Nature Genetics, which added fundamental new knowledge on the detection of subtelomeric rearrangements in patients with idiopathic MR. 116 Although this study is of significant importance, we were unable to include it in this review as the description of selection of patients was insufficient to provide reliable data on frequency of subtelomeric anomalies in unselected MR patients. Nor was it possible to determine the relation between yield of subtelomeric screening and clinical setting or specific characteristics of the studied group, such as MR severity and gender.…”

Clinical applications of two-color telomeric fluorescence in situ hybridization for prenatal diagnosis: Identification of chromosomal translocation in five families with recurrent miscarriages or a child with multiple congenital anomalies

“…Campana et al (1986) reported that a reciprocal translocation carrier was found by conventional cytogenetics technique in 181/5445 (3.3%) of the couples who had medical histories of recurrent abortions. On the other hand, Flint et al (1995) reported that three in 99 idiopathic mentally retarded patients with normal routine karyotypes had subtelomeric chromosomal rearrangements using hypervariable DNA polymorphism analysis. Cryptic translocations and deletions involving telomeric regions seem not to be uncommon in couples with multiple miscarriages or in families of an unexplained MCA/MR child.…”