Hydrocephalus With Hirschsprung Disease: Severe End of X-linked Hydrocephalus Spectrum
Hydrocephalus With Hirschsprung Disease: Severe End of X-linked Hydrocephalus Spectrum
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DOI：
10.1002/ajmg.a.35245
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发表时间：
2012-04-01
影响因子：
2
通讯作者：
Kosaki, Kenjiro
中科院分区：
文献类型：
--
作者：
Takenouchi, Toshiki;Nakazawa, Mie;Kosaki, Kenjiro
L1CAM分子是神经系统和肠道系统中的一种细胞黏附分子，与X-连锁脑积水(XLH)谱有关，X-连锁脑积水是一种罕见的疾病，具有严重的先天性脑积水、痂状体发育不良、智能障碍、痉挛和拇指内收。文献中已经报道了几例XLH合并先天性巨结肠症(HSCR)，但HSCR是由于XLH患者的功能获得突变(即新形性突变)所致，还是L1CAM突变谱的严重末端尚不清楚。本病例为日本男童，患有严重先天性脑积水，并伴有导水管狭窄及胼胝体发育不全。HSCR已经活检证实。L1CAM基因的突变分析显示，C61T突变位于外显子1，导致第21位氨基酸的无义突变截断，并产生一种极短的蛋白质，不太可能与其他蛋白质相互作用。这些发现表明，XLHHSCR代表了XLH谱的严重末端，而不是新形性突变。对于伴有严重便秘的XLH患者，应考虑进行彻底的腹部检查以排除HSCR。(C)2012年威利期刊公司。
L1CAM molecule is a cell adhesion molecule in nervous and enteric systems and is responsible for X-linked hydrocephalus (XLH) spectrum, which is a rare condition with severe congenital hydrocephalus, dysgenesis of the corpus callosum, intellectual disability, spasticity, and adducted thumbs. Several cases of XLH accompanied by Hirschsprung disease (HSCR) have been reported in the literature, but whether HSCR results from a gain-of-function mutation in cases with XLH, i.e., a neomorphic mutation, or the severe end of the L1CAM mutation spectrum remains unclear. The present patient was a Japanese boy with severe congenital hydrocephalus with aqueductal stenosis as well as hypoplasia of the corpus callosum. HSCR had been confirmed by a biopsy. A mutation analysis of the L1CAM gene showed a C61T mutation in exon 1, resulting in a truncating nonsense mutation at amino acid position 21 and producing an extremely short protein that was unlikely to interact with other proteins. These findings suggest that XLH-HSC Rrepresents the severe end of the XLH spectrum, rather than a neomorphic mutation. A thorough abdominal investigation to rule out HSCR should be considered in patients with XLH accompanied by severe constipation. (C) 2012 Wiley Periodicals, Inc.