Analysis For Subtelomeric Rearrangements In Mental Retardation/Developmental Delay Patients With Unknown Origin

Background:Mental retardation/Developmental delay,defined as a failure to develop a sufficient cognitive and adaptive level,affects approximately 1%to 3%of the general population. The epidemic study in 2000 showed that the prevalence rate of intelligence disability among 0-6yeas old children is 0.931%o,with an annual increase 136,000.2/3 patients are unkown origin. Over the past few years many studies have shown that subtelomeric rearrangement was one of the common reason of idiopathic MR/DD with figures varying from 5 to 10%.It has been recognized that the spectrum of clinical involvement about MR/DD is quite broad.The correlation between genotype and phenotype has been analyzed but no final conclusion up to now.In china,the datas of the subtelomeric rearrangements is very limited.Objective:To analysis the clinical characteristics and chromosome subtelomeres rearrangements in 378 patients with unexplained mental retardation/developmental delay which were collected in the Peking University First Hospital.To delineate genotype-phenotype correlation and to study the subtelomeric rearrangements rate in idiopathic MR/DD patients.To test the validity of our new diagnosis procedure for MR/DD.Methods:Clinical characteristics were analyzed in 378 patients with unexplained mental retardation/developmental delay.Informed consent was obtained from all the families tested before the study.DNA was extracted from peripheral blood lymphocytes and followed by Multiplex ligation-dependent probe amplification(MLPA) to analyse all chromosomes subtelomeres.Parents chromosome subtelomeres were analyzed if the proband has positive findings.Results:28 of 378 cases were identified with subtelomeric rearrangements(7.4%),including 18 cases with pure subtelomeric deletion(5 cases with 15pter del;4 cases with 4pter del;3 cases with 13pter del;2 cases with 11qter del;1 case with lpter del,1 case 7qter del,1 case 8pter del, 1 case 15qter del);3 cases with pure subtelomeric duplication(2 cases with 3qter dup;1 case with 22qter dup);5 cases both with subtelomeric deletion and duplication(2pter del+4pter dup, 7pter dup+8pter del,6qter dup+10pter del,9pter del+19pter dup,7pter del+12pter dup);2 case with two types subtelomeric deletion but at different position(13pter del+22qter del,14qter del+19qter del).The parents of 21 positive probands haven't found the same positive result in their children.The mother or father of the other 7 cases with positive results has been tested also, all were negative.Conclusions:The subtelomeric rearrangements were found in 7%patients with idiopathic MR/DD.It indicated that subtelomeric rearrangements should be one of major reasons of idiopathic MR/DD related to genetic factors.The spectrum of clinical involvement about MR/DD is so quite broad that we should screen for subtelomeric rearrangements in any patients with idiopathic MR/DD.Microdeletion is more common in subtelomeric rearrangements.MLPA is a promising technique to screen the subtelomedc rearrangements because of its simple effective fast and economic features.