Hyperphosphatasia-Mental Retardation Syndrome Due to PIGV Mutations: Expanded Clinical Spectrum
Hyperphosphatasia-Mental Retardation Syndrome Due to PIGV Mutations: Expanded Clinical Spectrum
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DOI：
10.1002/ajmg.a.34102
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发表时间：
2011-08-01
影响因子：
2
通讯作者：
Meinecke, Peter
中科院分区：
文献类型：
--
作者：
Horn, Denise;Krawitz, Peter;Meinecke, Peter
高磷酸酯酶症-智力低下综合征是最近描述的一种与可识别的面部表型和短指指骨相关的疾病。这种常染色体隐性遗传病是由 PIGV 的纯合和复合杂合错义突变引起的，PIGV 编码 GPI 锚定生物合成途径的成员。在这里，我们报告了另外两名不相关的患者，其中一名患者患有发育迟缓、血清 AP 水平升高、面部特征独特、末端指骨发育不全、肛门闭锁，另一名患者患有先天性巨结肠症。通过对 PIGV 进行测序，我们在患者 1 中检测到复合杂合突变 c.467G>A 和 c.1022C>A，在患者 2 中检测到纯合突变 c.1022C>A。我们回顾了已证实的 PIGV 突变的 8 例报告病例，并重新定义了与 PIGV 突变相关的表型谱：智力障碍、独特的面部完形、短肢畸形和磷酸酯酶过多症是恒定的特征，但肛门直肠畸形和先天性巨结肠以及唇/腭裂和听力障碍也应被视为临床谱的一部分。此外，癫痫发作和肌张力低下常常与 PIGV 突变相关。 (C) 2011 Wiley-Liss, Inc.
Hyperphosphatasia-mental retardation syndrome is a recently delineated disorder associated with a recognizable facial phenotype and brachytelephalangy. This autosomal recessive condition is caused by homozygous and compound heterozygous missense mutations of PIGV, encoding a member of the GPI-anchor biosynthesis pathway. Here, we report on two further, unrelated patients with developmental delay, elevated serum levels of AP, distinctive facial features, hypoplastic terminal phalanges, anal atresia in one and Hirschsprung disease in the other patient. By sequencing PIGV we detected compound heterozygous mutations c.467G>A and c.1022C>A in Patient 1 and a homozygous mutation c.1022C>A in Patient 2. We reviewed the eight reported cases with proven PIGV mutations and re-defined the phenotypic spectrum associated with PIGV mutations: intellectual disability, the distinct facial gestalt, brachytelephalangy, and hyperphosphatasia are constant features but also anorectal malformations and Hirschsprung disease as well as cleft lip/palate and hearing impairment should be considered as part of the clinical spectrum. Moreover, seizures and muscular hypotonia are frequently associated with PIGV mutations. (C) 2011 Wiley-Liss, Inc.