Subtelomeric aberrations in Thai patients with idiopathic mental retardation and autism detected by multiplex ligation-dependent probe amplification

Abstract

Background: Chromosomal rearrangements involving telomeres account for approximately 1%–30% of causes of mental retardation (MR). It is therefore recommended that all cases of undiagnosed MR be screened for subtelomeric aberration. Nevertheless, resolution of a standard karyotyping using the G-banding technique is limited. Therefore, an additional technique with higher resolution should be performed to detect this type of anomaly. Objectives: To screen for subtelomeric aberration in Thai patients with mental retardation and autism. Methods: Multiplex ligation-dependent probe amplification (MLPA), was used to screen 114 Thai patients with idiopathic MR and 15 patients with autism. All positive results were confirmed by using a different set of MLPA probes or real-time PCR. Results: We identified 5 patients with submicroscopic aberration in patients with MR. One patient had a submicroscopic deletion at the 1p36.33 region, which was confirmed by real-time PCR. There were 2 patients with subtelomeric duplication at the 15q11.2 and 11p15.5 regions sequentially. Two patients had the same duplication at the Xp22.33. region. Conclusions: The present study shows that the incidence of a subtelomeric aberration in Thai patients with idiopathic MR is approximately the same reported previously (3.9%). Identifying these submicroscopic aberrations requires an advanced method with higher resolution than standard karyotyping. Although microarray techniques may be a more informative, they are costly and require an array facility, which are not widely available, especially in developing countries. Thus, MLPA in a routine cytogenetic test for MR patients with normal karyotypes in this setting can help to increase diagnostic yield. Keywords: Autism, mental retardation, MLPA, subtelomere