Familial CHARGE syndrome because of CHD7 mutation:: clinical intra- and interfamilial variability
Familial CHARGE syndrome because of CHD7 mutation:: clinical intra- and interfamilial variability
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DOI：
10.1111/j.1399-0004.2007.00821.x
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发表时间：
2007-08-01
影响因子：
3.5
通讯作者：
Sanlaville, D.
中科院分区：
文献类型：
--
作者：
Delahaye, A.;Sznajer, Y.;Sanlaville, D.
CHARGE综合征（omim# 214800）是一种具有独特诊断标准的多发性畸形综合征，通常是因为CHD7（染色体结构解旋酶DNA结合7）单倍不足。CHARGE综合征的家族性发生是罕见的。我们报告了来自两个高加索家庭的6例患者（均为单亲和两个孩子），他们患有轻至重度CHARGE综合征。在这两个不相关的家庭中进行了CHD7基因的直接测序。在A家族中发现第一个染色体域的第8外显子突变（c.2501C > T - p.S834F），在b家族中发现第2外显子突变（c.469C > T - p.R157X），这两个突变在父母中都是新生的。A家族长子双侧唇腭裂、食管闭锁伴瘘、复杂心脏缺损、椎体畸形，小儿子后结肠。他们的母亲有无症状的前庭功能障碍和视网膜缺损，在她的孩子的分子诊断后确定。在B家庭中，两名患儿均有严重的CHARGE综合征表达。携带突变基因的父亲只有鼻翼不对称异常。这些家族性报告描述了CHARGE综合征的家族内变异性，并强调在不符合CHARGE综合征“经典临床标准”的患者中存在CHD7突变。
CHARGE syndrome (OMIM #214800) is a multiple malformation syndrome with distinctive diagnostic criteria, usually because of CHD7 (chromodomain helicase DNA binding 7) haploinsufficiency. Familial occurrence of CHARGE syndrome is rare. We report six patients from two Caucasian families (both with one parent and two children) affected by mild to severe CHARGE syndrome. Direct sequencing of the CHD7 gene was performed in these two unrelated families. A mutation in exon 8 (c.2501C > T - p.S834F) in first chromodomain was found in family A and a nonsense mutation in exon 2 (c.469C > T - p.R157X) in family B. Both mutations are de novo in the parents. In family A, the elder son had bilateral cleft lip and palate, esophageal atresia with fistula, complex heart defect and vertebral abnormalities, while the younger had a posterior coloboma. Their mother had asymptomatic vestibular dysfunction and retinal coloboma, identified after the molecular diagnosis of her children. In family B, both affected children had severe expression of CHARGE syndrome. The father carrying the mutation only had asymmetric anomaly of the pinnae. These familial reports describe the intrafamilial variability of CHARGE syndrome, and underline the presence of CHD7 mutations in patients who do not fit the 'classical clinical criteria' for CHARGE syndrome.