CHARGE syndrome:: the phenotypic spectrum of mutations in the CHD7 gene
CHARGE syndrome:: the phenotypic spectrum of mutations in the CHD7 gene
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DOI：
10.1136/jmg.2005.036061
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发表时间：
2006-04-01
影响因子：
4
通讯作者：
van Ravenswaaij, CMA
中科院分区：
文献类型：
--
作者：
Jongmans, MCJ;Admiraal, RJ;van Ravenswaaij, CMA
背景：CHARGE综合征是一种非随机聚类的先天性异常，包括结肠瘤、心脏缺陷、后肛门闭锁、生长发育迟缓、生殖器发育不全、耳部异常和耳聋。CHARGE综合征的一个一致特征是半规管发育不全导致前庭反射。其他常见的先天性异常包括面神经麻痹、唇腭裂和气管食管瘘。具体的行为问题，包括自闭症样行为，已经被描述。染色体8q12.1上的CHD7基因最近被发现是参与该综合征病因学的主要基因。方法：对107例具有CHARGE综合征临床特征的指标患者进行CHD7编码区突变筛选。采集突变阳性患者的临床资料，研究CHD7基因突变的表型谱。结果：69例患者中发现了突变。在这里，我们描述了47例患者的临床特征，包括两对兄弟姐妹。大多数突变是独特的，分散在整个基因中。除1例患者外，所有患者均符合当前CHARGE综合征的诊断标准。在这个队列中没有明显的基因型-表型相关性，这最好地证明了具有相同突变的兄弟姐妹在临床表现上的差异。在一对兄弟姐妹的未受影响的母亲中检测到体细胞嵌合体，支持种系嵌合体的存在。结论：CHD7突变占CHARGE综合征病例的大多数，具有广泛的临床变异性，无明显的基因型-表型相关性。在一个案例中，提供了生殖系嵌合现象的证据。
Background: CHARGE syndrome is a non-random clustering of congenital anomalies including coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear anomalies, and deafness. A consistent feature in CHARGE syndrome is semicircular canal hypoplasia resulting in vestibular areflexia. Other commonly associated congenital anomalies are facial nerve palsy, cleft lip/palate, and tracheo-oesophageal fistula. Specific behavioural problems, including autistic-like behaviour, have been described. The CHD7 gene on chromosome 8q12.1 was recently discovered as a major gene involved in the aetiology of this syndrome.Methods: The coding regions of CHD7 were screened for mutations in 107 index patients with clinical features suggestive of CHARGE syndrome. Clinical data of the mutation positive patients were sampled to study the phenotypic spectrum of mutations in the CHD7 gene.Results: Mutations were identified in 69 patients. Here we describe the clinical features of 47 of these patients, including two sib pairs. Most mutations were unique and were scattered throughout the gene. All patients but one fulfilled the current diagnostic criteria for CHARGE syndrome. No genotype-phenotype correlations were apparent in this cohort, which is best demonstrated by the differences in clinical presentation in sib pairs with identical mutations. Somatic mosaicism was detected in the unaffected mother of a sib pair, supporting the existence of germline mosaicism.Conclusions: CHD7 mutations account for the majority of the cases with CHARGE syndrome, with a broad clinical variability and without an obvious genotype-phenotype correlation. In one case evidence for germline mosaicism was provided.