Vuorela Pia E, Penttinen Maila T, Hietala Marja H, Laine Jukka O, Huoponen Kirsi A, Kääriäinen Helena A
The Department of Medical Genetics, University of Turku, Turku, Finland.
Clin Dysmorphol. 2008 Oct;17(4):249-53. doi: 10.1097/MCD.0b013e328306a704.
The autosomal dominant CHARGE syndrome (MIM musical sharp214800) is caused by mutations in the CHD7 gene. It is usually sporadic but a few cases with gonadal mosaicism and familial inheritance have been reported. We describe a familial CHARGE syndrome in a two-generation Finnish family with a nonsense mutation in the CHD7 gene. Detailed clinical examination of the affected family members was performed, and mutations in the CHD7 gene were analysed with direct sequencing and multiplex ligation-dependent probe amplification. A nonsense mutation, p.Q1599X, was detected in exon 21 of the CHD7 gene in three affected family members. The father was only mildly affected, whereas his son had a very severe manifestation of the syndrome, causing death at the age of 3 months. The second pregnancy was prematurely terminated in the 23rd week because of cardiac anomalies detected in the ultrasound scan. The father's brother also had mild symptoms, but no mutation was detected in him. In this report, the variability of clinical symptoms within families and the clinical importance of mildly affected patients with the CHARGE syndrome are underlined with implications for molecular genetic diagnostics of the syndrome. Features not described in the CHARGE syndrome before are also presented.
常染色体显性遗传的CHARGE综合征（MIM编号214800）由CHD7基因突变引起。该病通常为散发性，但也有少数关于生殖腺嵌合体和家族遗传的病例报道。我们描述了一个芬兰两代家族中的家族性CHARGE综合征，该家族的CHD7基因存在一个无义突变。对受影响的家族成员进行了详细的临床检查，并采用直接测序和多重连接依赖探针扩增技术分析了CHD7基因的突变情况。在三名受影响的家族成员中，检测到CHD7基因第21外显子存在一个无义突变p.Q1599X。父亲仅受到轻度影响，而他的儿子则出现了该综合征非常严重的症状，在3个月大时死亡。由于超声检查发现心脏异常，第二次怀孕在第23周时提前终止。父亲的兄弟也有轻微症状，但未在他身上检测到突变。在本报告中，强调了家族内临床症状的变异性以及CHARGE综合征轻度受影响患者的临床重要性，这对该综合征的分子遗传学诊断具有启示意义。同时还介绍了以前CHARGE综合征中未描述的特征。
