Submicroscopic subtelomeric aberrations in Chinese patients with unexplained developmental delay/mental retardation

Abstract

BackgroundSubtelomeric imbalance is widely accepted as related to developmental delay/mental retardation (DD/MR). Fine mapping of aberrations in gene-enriched subtelomeric regions provides essential clues for localizing critical regions, and provides a strategy for identifying new candidate genes. To date, no large-scale study has been conducted on subtelomeric aberrations in DD/MR patients in mainland China.MethodsThis study included 451 Chinese children with moderate to severe clinically unexplained DD/MR. The subtelomere-MLPA (multiplex ligation dependent probe amplification) and Affymetrix human SNP array 6.0 were used to determine the subtelomeric copy number variations. The exact size and the breakpoint of each identified aberration were well defined.ResultsThe submicroscopic subtelomeric aberrations were identified in 23 patients, with a detection rate of 5.1%. 16 patients had simple deletions, 2 had simple duplications and 5 with both deletions and duplications. The deletions involved 14 different subtelomeric regions (1p, 2p, 4p, 6p, 7p, 7q, 8p, 9p, 10p, 11q, 14q, 15q, 16p and 22q), and duplications involved 7 subtelomeric regions (3q, 4p, 6q, 7p, 8p, 12p and 22q). Of all the subtelomeric aberrations found in Chinese subjects, the most common was 4p16.3 deletion. The sizes of the deletions varied from 0.6 Mb to 12 Mb, with 5-143 genes inside. Duplicated regions were 0.26 Mb to 11 Mb, with 6-202 genes inside. In this study, four deleted subtelomeric regions and one duplicated region were smaller than any other previously reported, specifically the deletions in 11q25, 8p23.3, 7q36.3, 14q32.33, and the duplication in 22q13. Candidate genes inside each region were proposed.ConclusionsSubmicroscopic subtelomeric aberrations were detected in 5.1% of Chinese children with clinically unexplained DD/MR. Four deleted subtelomeric regions and one duplicated region found in this study were smaller than any previously reported, which will be helpful for further defining the candidate dosage sensitive gene associated with DD/MR.

Detection of chromosomal imbalances using combined MLPA kits in patients with syndromic intellectual disability

“…In four patients (case 4, 5, 6 and 10) with normal karyotype results (4/13, 30.7%) we detected both a deletion and a duplication, which suggests the presence of a cryptic unbalanced translocation. This prevalence is within the range of 21.7-42.1% reported in previous studies (7,19,21).…”

“…Previously reported studies that performed subtelomere analysis showed an overall abnormality rate of 6%, varying between different studies from 2 to 29% (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). The reasons for these differences are the inclusion criteria and the assay used in the study, the size of the cohort and the complete exclusion (or not) of the polymorphisms.…”

Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes

“…For the last three patients with 2pter deletion reported in the literature, clinical information was unavailable. 3,5 Clinical features of the patients reported in the literature are listed in Table 2.…”

“…[1][2][3][4][5][6][7][8] Becker et al 6 reported a patient with a de novo pure 2p25.2 deletion, bilateral severe talipes equinovarus, pulmonary valve stenosis, nasal polyps, mild psychomotor retardation, and overweightness with food seeking behaviour. Several patients were then reported presenting with obesity, intellectual disability (ID), and 2p25 deletion.…”

Karyotype-Phenotype Correlation in Partial Trisomies of the Short Arm of Chromosome 6: A Family Case Report and Review of the Literature

“…Reviewing a published series on prenatal diagnosis and cytogenetic analysis revealed a 6p duplication recurrence rate of approximately 1-2 cases on 10,000 investigations [Ravnan et al, 2006;Lee et al, 2012;Shaffer et al, 2012]. Carriers of 6p trisomy can also be identified among patients who underwent cytogenetic investigations because of mental retardation [Anderlid et al, 2002], developmental delay and intellectual disabilities [Roberts et al, 2004;Belligni et al, 2009;Wu et al, 2010]. Nonetheless, it is difficult to calculate realistic rates of prevalence or incidence.…”