伴有牙齿异常及新型WNT7A突变的阿尔-阿瓦迪-拉斯-罗斯柴尔德综合征
Al-Awadi-Raas-Rothschild syndrome with dental anomalies and a novel WNT7A mutation.
作者信息
Kantaputra Piranit Nik, Kapoor Seema, Verma Prashant, Kaewgahya Massupa, Kawasaki Katsushige, Ohazama Atsushi, Ketudat Cairns James R
机构信息
Center of Excellence in Medical Genetics Research, Chiang Mai University, Chiang Mai, Thailand; Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand; Dentaland Clinic, Chiang Mai, Thailand.
Pediatrics Research & Genetic Lab, Department of Pediatrics, MAMC & Associated Lok Nayak Hospital, New Delhi, India.
出版信息
Eur J Med Genet. 2017 Dec;60(12):695-700. doi: 10.1016/j.ejmg.2017.09.005. Epub 2017 Sep 14.
Al-Awadi-Raas-Rothschild syndrome (AARRS; OMIM 276820) is a very rare autosomal recessive limb malformation syndrome caused by WNT7A mutations. AARRS is characterized by various degrees of limb aplasia and hypoplasia. Normal intelligence and malformations of urogenital system are frequent findings. Complete loss of WNT7A function has been shown to cause AARRS, however, its partial loss leads to the milder malformation, Fuhrmann syndrome. An Indian boy affected with AARRS is reported. A novel homozygous base substitution mutation c.550A > C (p.Asn184Asp) is identified in the patient. Parents were heterozygous for the mutation. In addition to the typical features of AARRS, the patient had agenesis of the mandibular left deciduous lateral incisor. The heterozygous parents had microdontia of the maxillary left permanent third molar and taurodontism (enlarged dental pulp chamber at the expense of root) in a number of their permanent molars. Whole exome sequencing of the patient and his parents ruled out mutations in 11 known hypodontia-associated genes including WNT10A, MSX1, EDA, EDAR, EDARADD, PAX9, AXIN2, GREM2, NEMO, KRT17, and TFAP2B. In situ hybridization during tooth development showed Wnt7a expression in wild-type tooth epithelium at E14.5. All lines of evidence suggest that WNT7A has important role in tooth development and its mutation may lead to tooth agenesis, microdontia, and taurodontism. Oral examination of patients with AARRS and Fuhrmann syndromes is highly recommended.
阿瓦迪 - 拉斯 - 罗斯柴尔德综合征(AARRS;OMIM 276820)是一种由WNT7A基因突变引起的非常罕见的常染色体隐性肢体畸形综合征。AARRS的特征是不同程度的肢体发育不全和发育不良。常伴有智力正常和泌尿生殖系统畸形。已证实WNT7A功能完全丧失会导致AARRS,然而,其部分丧失会导致较轻微的畸形,即富尔曼综合征。本文报道了一名患AARRS的印度男孩。在该患者中鉴定出一种新的纯合碱基替换突变c.550A>C(p.Asn184Asp)。父母为该突变的杂合子。除了AARRS的典型特征外,该患者还患有左下颌乳侧切牙缺失。杂合子父母的左上颌恒第三磨牙过小,并且他们的一些恒磨牙存在牛牙样牙(以牺牲牙根为代价的牙髓腔扩大)。对患者及其父母进行的全外显子组测序排除了11个已知的与少牙相关基因的突变,这些基因包括WNT10A、MSX1、EDA、EDAR、EDARADD、PAX9、AXIN2、GREM2、NEMO、KRT17和TFAP2B。牙齿发育过程中的原位杂交显示,在E14.5时野生型牙齿上皮中有Wnt7a表达。所有证据表明,WNT7A在牙齿发育中起重要作用,其突变可能导致牙齿缺失、过小牙和牛牙样牙。强烈建议对AARRS和富尔曼综合征患者进行口腔检查。