Clinical manifestations of the deletion of Down syndrome critical region including DYRK1A and KCNJ6.

A relatively small region of human chromosome 21 (Hsa21) is considered to play a major role in Down syndrome (DS) phenotypes, and the concept of a Down syndrome critical region (DSCR) has been proposed. The goal of the phenotype-genotype correlation study is to discover which genes are responsible for each DS phenotype. Loss of the genomic copy numbers of Hsa21 can give us important suggestion to understand the functions of the involved genes. Genomic copy number aberrations were analyzed by micro-array-based comparative genomic hybridization (aCGH) in 300 patients with developmental delay. Partial deletions of Hsa21 were identified in three patients with developmental delay, epilepsy, microcephaly, and distinctive manifestations. Two of the patients had mosaic deletions of 21q22-qter including a part of DSCR; one of whom whose mosaic ratio was higher than the other showed more severe brain morphogenic abnormality with colpocephaly, which was similar to the previously reported patients having pure deletions of 21q22-qter, indicating the critical region for cortical dysplasia at this region. The remaining patient had the smallest microdeletion with 480 kb in DSCR including DYRK1A and KCNJ6. Although we could not identify any nucleotide alteration in DYRK1A and KCNJ6 in our cohort study for 150 patients with mental retardation with/without epilepsy, this study underscores the clinical importance of DSCR not only for DS but also for developmental disorders.