A 4q35.2 subtelomeric deletion identified in a screen of patients with co-morbid psychiatric illness and mental retardation

Abstract

Background: Cryptic structural abnormalities within the subtelomeric regions of chromosomes have been the focus of much recent research because of their discovery in a percentage of people with mental retardation (UK terminology: learning disability). These studies focused on subjects (largely children) with various severities of intellectual impairment with or without additional physical clinical features such as dysmorphisms. However it is well established that prevalence of schizophrenia is around three times greater in those with mild mental retardation. The rates of bipolar disorder and major depressive disorder have also been reported as increased in people with mental retardation. We describe here a screen for telomeric abnormalities in a cohort of 69 patients in which mental retardation co-exists with severe psychiatric illness.

Methods: We have applied two techniques, subtelomeric fluorescence in situ hybridisation (FISH) and multiplex amplifiable probe hybridisation (MAPH) to detect abnormalities in the patient group.

Results: A subtelomeric deletion was discovered involving loss of 4q in a patient with co-morbid schizoaffective disorder and mental retardation.

Conclusion: The precise region of loss has been defined allowing us to identify genes that may contribute to the clinical phenotype through hemizygosity. Interestingly, the region of 4q loss exactly matches that linked to bipolar affective disorder in a large multiply affected Australian kindred.

Figure 1

Subtelomeric region of chromosome 4q Only annotated, unique chromosome sequence is shown, derived from the November 2002 version of the UCSC Human Genome assembly (subtelomeric repeats would extend to the right of the diagram). A scale bar and the gene content (see Table 2) of the region are shown. The positions of the MAPH markers are also shown which allowed the maximum and minimum extents of the deletion to be defined (black bar). Above the chromosome region is shown the result of duplicate analysis from each MAPH probe (mean +/- 95% CI), together with the 3 standard deviation threshold and the results from the other control probes (mean +/- 95% CI).