J Hum Genet. 2014 Oct;59(10):581-3. doi: 10.1038/jhg.2014.71. Epub 2014 Aug 7.

A girl with West syndrome and autistic features harboring a de novo TBL1XR1 mutation.


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.


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.

PMID:  25102098