Abstract:

Recently, de novo mutations in TBL1XR1 were found in two patients with autism spectrum disorders. Here, we report on a Japanese girl presenting with West syndrome, Rett syndrome-like and autistic features. Her initial development was normal until she developed a series of spasms at 5 months of age. Electroencephalogram at 7 months showed a pattern of hypsarrhythmia, which led to a diagnosis of West syndrome. Stereotypic hand movements appeared at 8 months of age, and autistic features such as deficits in communication, hyperactivity and excitability were observed later, at 4 years and 9 months. Whole exome sequencing of the patient and her parents revealed a de novo TBL1XR1 mutation [c.209 G>A (p.Gly70Asp)] occurring at an evolutionarily conserved amino acid in an F-box-like domain. Our report expands the clinical spectrum of TBL1XR1 mutations to West syndrome with Rett-like features, together with autistic features.

日本語要旨:

最近，TBL1XR1におけるde novo変異が2名の自閉症スペクトラム疾患に見つかった．この論文は，west症候群，Rett症候群様症状，自閉症的特徴を示した日本人女児についての報告である．5か月時に一連の発作を起こすまでは正常発達であった．7か月時の脳波でヒプスアリスミアを認め，west症候群と診断した．8か月時に常同的な手の動きが出現し，その後，4歳9か月時にはコミュニケーション障害等の自閉症的な特徴，多動，易興奮性を認めた．患児と両親の全エクソーム解析では， F box様領域の進化的に保存されているアミノ酸に生じたTBL1XR1のde novo変異［c.209G>A (p.Gly70Asp)］を認めた．TBL1XR1変異により，自閉症的な特徴をもち，Rett症候群様症状を呈するWest症候群を起こしうる．