Zweier C, Sticht H, Bijlsma E K, Clayton-Smith J, Boonen S E, Fryer A, Greally M T, Hoffmann L, den Hollander N S, Jongmans M, Kant S G, King M D, Lynch S A, McKee S, Midro A T, Park S-M, Ricotti V, Tarantino E, Wessels M, Peippo M, Rauch A
J Med Genet. 2008 Nov;45(11):738-44. doi: 10.1136/jmg.2008.060129. Epub 2008 Aug 26.
Haploinsufficiency of the gene encoding for transcription factor 4 (TCF4) was recently identified as the underlying cause of Pitt-Hopkins syndrome (PTHS), an underdiagnosed mental-retardation syndrome characterised by a distinct facial gestalt, breathing anomalies and severe mental retardation.
TCF4 mutational analysis was performed in 117 patients with PTHS-like features.
In total, 16 novel mutations were identified. All of these proven patients were severely mentally retarded and showed a distinct facial gestalt. In addition, 56% had breathing anomalies, 56% had microcephaly, 38% had seizures and 44% had MRI anomalies.
This study provides further evidence of the mutational and clinical spectrum of PTHS and confirms its important role in the differential diagnosis of severe mental retardation.
最近发现，编码转录因子4（TCF4）的基因单倍剂量不足是皮特-霍普金斯综合征（PTHS）的根本病因，这是一种诊断不足的智力发育迟缓综合征，其特征为独特的面部形态、呼吸异常和严重智力发育迟缓。
对117例具有PTHS样特征的患者进行了TCF4突变分析。
共鉴定出16种新突变。所有这些确诊患者均有严重智力发育迟缓，并表现出独特的面部形态。此外，56%的患者有呼吸异常，56%的患者有小头畸形，38%的患者有癫痫发作，44%的患者有MRI异常。
本研究为PTHS的突变和临床谱提供了进一步证据，并证实了其在重度智力发育迟缓鉴别诊断中的重要作用。
