Abstract:

The 22q13.3 deletion syndrome is characterized by a significant delay in language development, mental retardation, hypotonia, and autistic features. Cumulative evidence has shown that haploinsufficiency of the SHANK3 gene is a major cause of the neurological symptoms of the 22q13.3 deletion syndrome. Shank3, a multidomain protein containing the SH3 and PDZ domains, is thought to play an important role in the formation and function of synapses in the developing brain. In this study, we analyzed the SHANK3 gene in 128 autistic patients with manifestations similar to those seen in the 22q13.3 deletion syndrome. The results showed a 6-amino acid deletion upstream of the SH3 domain, a missense variant (arginine to histidine at amino acid position 656) in the PDZ domain, and the insertion or deletion of a repeated 10-bp GC sequence located 9-bp downstream from the 3' end of exon 11. None of these variants was found in 228 controls.

日本語要旨:

重度言語障害・精神遅滞を呈する自閉症患者百数十例におけるゲノム解析から、自閉症関連遺伝子であるSHANK3遺伝子に複数の変異を見いだした。本論文は、DNAメチル化に関与するCpG islandや蛋白質相互作用に重要なPDZドメイン等機能領域における初めての遺伝子変異報告である。