Delahaye A, Sznajer Y, Lyonnet S, Elmaleh-Bergès M, Delpierre I, Audollent S, Wiener-Vacher S, Mansbach A-L, Amiel J, Baumann C, Bremond-Gignac D, Attié-Bitach T, Verloes A, Sanlaville D
Medical Genetics Department, Robert Debré University Hospital, Paris, France.
Clin Genet. 2007 Aug;72(2):112-21. doi: 10.1111/j.1399-0004.2007.00821.x.
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.
CHARGE综合征（OMIM #214800）是一种具有独特诊断标准的多重畸形综合征，通常由CHD7（染色质结构域解旋酶DNA结合蛋白7）单倍体不足引起。CHARGE综合征的家族性发病较为罕见。我们报告了来自两个高加索家庭的6名患者（每个家庭均为父母一方和两个孩子），他们患有轻度至重度的CHARGE综合征。对这两个无亲缘关系的家庭进行了CHD7基因的直接测序。在A家族中发现第1个染色质结构域的外显子8发生突变（c.2501C>T - p.S834F），在B家族中发现外显子2发生无义突变（c.469C>T - p.R157X）。这两个突变在父母中均为新发突变。在A家族中，大儿子患有双侧唇腭裂、食管闭锁伴瘘管、复杂心脏缺陷和椎体异常，而小儿子患有后巩膜葡萄肿。他们的母亲在其子女进行分子诊断后，被发现有无症状前庭功能障碍和视网膜缺损。在B家族中，两个患病孩子均有CHARGE综合征的严重表现。携带突变的父亲仅有耳廓不对称异常。这些家族报告描述了CHARGE综合征的家族内变异性，并强调了在不符合CHARGE综合征“经典临床标准”的患者中存在CHD7突变。
