Abstract: Objective： Combined using MLPA and Affymetrix SNP 6.0 chip to detect and fine mapping subtelomeric rearrangement in patients with unexplained MR/DD, finally to provide new methods and evidence for the etiologic diagnosis of MR/DD in China. Methods： 1. Collect unexplained MR/DD patients, 2.MLPA combined with Affymetrix SNP 6.0 chip was performed to detect and fine mapping subtelomeric rearrangements in patients. Results：The subtelomeric aberrations were identified in 41 patients, with a detection rate of 6.5%. 30 patients had simple deletions, 6 had simple duplications and 5 with both deletions and duplications. The sizes of the deletions varied from 0.6 to 12 Mb, with 5-202 genes inside. Duplicated regions were 0.26 to 11 Mb, with 6-143 genes inside. Compare with the MLPA negative patients, the incidence of appearance malformations（75.6%） and other congenital malformations（51.2%） are significantly higher in the MPLA positive patients（P<0.05）. Conclusions： Subtelomeric copy number variation is an important cause of unexplained MR/DD. Four deleted subtelomeric regions and one duplicated region found were smaller than any previously reported, which will be helpful for further defining the candidate dosage sensitive gene associated with MD/DD. Subtelomeric aberrations were detected in 6.5% of Chinese children with unexplained MR/DD. 5 complex subtelomeric aberretions have not been reported. Four deleted subtelomeric regions and one duplicated region found were smaller than any previously reported, which will be helpful for further defining the candidate dosage sensitive gene associated with MR/DD.

Key words: Mental retardation, Developmental disabilities, Telomere, Gene deletion, Gene rearrangement