IMPAD1 Mutations in Two Catel-Manzke Like Patients
IMPAD1 Mutations in Two Catel-Manzke Like Patients
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DOI：
10.1002/ajmg.a.35504
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发表时间：
2012-09-01
影响因子：
2
通讯作者：
Cormier-Daire, Valerie
中科院分区：
文献类型：
--
作者：
Nizon, Mathilde;Alanay, Yasemin;Cormier-Daire, Valerie
Catel-Manzke综合征的特征是多指畸形伴双侧食指偏斜和小颌畸形伴或不伴腭裂。一些非典型的患者表现为额外的畸形。目前还没有分子基础。大多数患者有一个不显着的家族史，但常染色体隐性遗传最近已被建议在一个近亲家族复发的同胞。Catel-Manzke综合征与CANT 1（钙激活核苷酸酶1）突变导致的Desbuquois发育不良1型以及最近在4例患者中报告的IMPAD 1（含肌醇单磷酸酶1结构域）突变导致的“软骨发育不良伴关节脱位，gPAPP型”具有重叠特征，所有患者均以身材矮小、关节脱位、短指和腭裂为特征。我们研究的目的是在Catel-Manzke患者中筛选CANT 1和IMPAD 1。根据其他特征的存在，3名患者被诊断为经典Catel-Manzke综合征，2名患者被诊断为Catel-Manzke样患者。我们在两名Catel-Manzke样患者中鉴定出两个纯合的IMPAD 1功能丧失突变（p.Arg187X和p.Ser108ArgfsX48）。其表型特征为严重生长迟缓伴四肢短小畸形、腭裂伴小颌畸形和膝关节过度松弛。手和脚的X光片显示许多副骨，指骨和腕关节骨性结合异常。根据本报告，我们得出的结论是，应对患有Catel-Manzke和其他特征的患者进行IMPAD 1筛查。(C)2012 Wiley Periodicals，Inc.
Catel-Manzke syndrome is characterized by hyperphalangism with bilateral deviation of the index fingers and micrognathia with or without cleft palate. Some atypical patients present with additional malformations. No molecular basis is yet available. Most patients have an unremarkable family history but autosomal recessive inheritance has been recently suggested in a consanguineous family with recurrence in sibs. Catel-Manzke syndrome has overlapping features with Desbuquois dysplasia type 1 due to CANT1 (calcium-activated nucleotidase 1) mutations and also with "chondrodysplasia with joint dislocations, gPAPP type" due to IMPAD1 (Inositol Monophosphatase Domain containing 1) mutations recently reported in four patients, all characterized by short stature, joint dislocations, brachydactyly and cleft palate. The aim of our study was to screen CANT1 and IMPAD1 in Catel-Manzke patients. Three patients were diagnosed as classical Catel-Manzke syndrome and two as Catel-Manzke like patients, based on the presence of additional features. We identified two homozygous loss-of-function IMPAD1 mutations in the two Catel-Manzke like patients (p.Arg187X and p.Ser108ArgfsX48). The phenotype was characterized by severe growth retardation with short and abnormal extremities, cleft palate with micrognathia and knee hyperlaxity. Radiographs of hands and feet revealed numerous accessory bones with abnormally shaped phalanges and carpal synostosis. Based on this report, we concluded that IMPAD1 should be screened for patients with Catel-Manzke and additional features. (C) 2012 Wiley Periodicals, Inc.