Mental retardation (MR) is one of the challenging clinically important disorders for which the ediopathogenesis in more than 50% of the cases remain poorly understood. MR has been defined as a significant impairment of cognitive and adaptive function, with onset before age 18 years. It is a life-long disability condition that has enormous burdens to affected family and society, and has been posing a great challenge for genetic counseling. Advances in molecular cytogenetics have played an increasing important role in the research and diagnosis of MR. Recently, microarray CGH has becoming a powerful diagnostic tool for detection of genomic imbalances associated with unexplained MR. It is our goal in this research proposal to complete a genomic imbalance study using genomewide oligonucleotide array CGH in a cohort of 195 MR individual from a mental retardation and rehabilitation center in Taiwan. These MR individuals were selected from 242 MR patients in the center under the previous grant project to rule out having any numerical or structural chromosome aberrations detected by conventional cytogenetic study, or having subtelomeric imbalance, deletion and duplication syndromes associate with MR detected by multiplex ligation-dependent probe amplification (MLPA) and subtelomeric FISH. A genomewide oligonucleotide array CGH study will then be conducted to investigate the genomic imbalance in the form of copy number variation (CNV) associated with MR in these selected MR cases. Due to the high cost of oligonucleotide array CGH kit, we plan to perform array CGH study on 20-30 MR cases in my previously funded project and will undertake the array CGH study on 100 MR cases in this proposed study (expected to complete the remaining ~70 cases in the third year). It is our hope that the study will shed more light on the cause of idiopathic mental retardation, as identification of the submicroscopic deletion or duplication or genes may cause mental deficiency and retardation. Furthermore, various CNV detected among the MR individual in proposed study will provide a better understanding regarding so called benign CNV or pathogenic CNV and will be very useful for future ascertainment of the clinical significance of CNV in Taiwanese mental retardation populations.
