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Novel variants of the SHANK3 gene in Japanese autistic patients with severe delayed speech development

Waga, Chikakoa; Okamoto, Nobuhikoc; Ondo, Yumikoa; Fukumura-Kato, Reikoa; Goto, Yu-ichib; Kohsaka, Shinichia; Uchino, Shigeoa

doi: 10.1097/YPG.0b013e328341e069
Brief Report

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.

aDepartments of Neurochemistry

bMental Retardation and Birth Defect Research, National Institute of Neuroscience, Tokyo

cDepartment of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan

Correspondence to Shinichi Kohsaka, MD, PhD, Department of Neurochemistry, National Institute of Neuroscience, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan Tel: +81 42 346 1711; fax: +81 42 346 1741; e-mail:

Received March 17, 2010

Accepted October 21, 2010

© 2011 Lippincott Williams & Wilkins, Inc.