OFD1基因突变引起的Joubert综合征10型一例临床和基因分析

Clinical and genetic analysis of a family with Joubert syndrome type 10 caused by OFD1 gene mutation

目的对Joubert综合征进行临床特点和遗传学分析。方法对2015年8月山东大学齐鲁儿童医院呼吸介入科临床疑为Joubert综合征的1例患儿进行临床及实验室检查，并应用新一代测序技术，对该患儿及其父母进行分子遗传学分析。结果患儿男，3月龄21d，因咳嗽、气喘1月余就诊，头颅磁共振成像显示中脑似呈“磨牙状”，查体发现手足均为六指畸形，四肢短小，视盘缺损、脉络膜缺损，内脏反位。基因检测发现定位于染色体xp22．2的OFD1基因存在缺失突变（c．2843_2844delAA）为新生突变，其父母均未携带该突变，该突变可致OFD1蛋白由972氨基酸截断为948氨基酸。结论本患儿临床表现为多器官发育不良，基因检测OFDl存在移码突变c．2843_2844delAA．临床分析结合基因检测结果，可明确诊断该患儿为罕见的Joubert综合征10型。

Objective To investigate the genetic cause for a family with muhiorgan dysplasia and ＂molar tooth sign＂ on MRI image. Method The patient,a 3 months and 21 days old boy, was clinically examined and the medical history of his family was collected. Next generation sequencing was performed to analyze his clinical and genetic causes. Result Clinical manifestation of the child displayed multiorgan dysplasia, such as six finger deformity, short limbs, coloboma of optic disc and choroid, situs inversus. Cranial MRI showed ＂molar tooth sign＂. The gene sequencing confirmed that the child carried a de novo deletion of c. 2843_2844 delAA in OFD1 gene. Conclusion The child has typical clinical features of Joubert syndrome, such as MRI ＂molar syndrome＂, developmental abnormalities of ocular tissue and limb, visceral inversion, and so on. The OFD1 gene had a novel deletion mutation through gene detection. Combined clinical features with gene detection, it was clear that the child was a rare case of Joubert syndrome type 10 which was the first case of ]oubert syndrome caused by OFD1 gene mutation in China.