1个Alagille综合征家系中JAG1基因新突变的识别

Alagille综合征 （ALGS）是一种主要由JAG1基因突变导致的常染色体显性遗传病，可累及肝脏、心脏、骨骼、眼和面部等多器官。本文报道1例ALGS患儿的临床和遗传学特征。患儿，男，2岁9个月，因发现肝功能异常及心脏杂音2年余就诊。查体：发育营养稍差，皮肤巩膜无黄染。前额突起，左眼内斜视，鼻梁低平，小下颌。双肺呼吸音清，胸骨左缘2~3肋间可闻及2/6级收缩期杂音，肝脾不大。血生化发现胆汁酸、胆红素、转氨酶等均升高。心脏彩超提示房间隔缺损 （静脉窦型）和左肺动脉狭窄；脊柱正位片发现第6、8胸椎蝴蝶椎畸形。患儿明显左眼内斜，眼科诊断眼球后退综合征。因此，该患儿符合ALGS在肝脏、心脏、脊柱和面部的特殊表现，且DNA直接测序发现JAG1基因存在一个新突变c.2419delG （p.Glu807AsnfsX819），ALGS诊断明确。确诊后予以对症支持治疗。目前已随访至4岁2个月，病情平稳，但面部畸形、左眼内斜视、心脏杂音和肝功能异常持续存在，其远期预后有待观察。

Identification of a novel JAG1 mutation in a family affected by Alagille syndrome

Alagille syndrome (ALGS) is an autosomal dominant disorder which is mainly caused by JAG1 gene mutation and can affect multiple systems including the liver, heart, eyes, skeleton and face. This paper reports the clinical and genetic features of an ALGS patient. A 2-year-and-9-month-old boy was referred to the hospital with the complaint of abnormal liver function and heart murmur discovered over two years. Jaundice of the skin and sclera was not observed. The child had a prominent forehead, left esotropia, depressed nasal bridge and micromandible. The two lungs were clear on auscultation, but a systolic cardiac murmur of grade 2/6 could be heard between the 2nd and 3rd intercostal space at the left sternal border. Neither abdominal distension nor enlarged liver or spleen was discovered. X-ray radiography uncovered butterlfy malformation of the 6th and 8th thoracic vertebrae. Serum biochemistry analysis revealed elevation of total bile acids, bilirubin and transaminases. Based on the clinical characteristics and the consultation opinion of the ophthalmologist, the child was diagnosed to have ALGS with Duane retraction syndrome. DNA direct sequencing detected a novel JAG1 mutation c.2419delG(p.Glu807AsnfsX819) in the child. Symptomatic and supportive therapy was performed thereafter and clinical follow-up was conducted until he was 4 years and 2 months. In the follow-up visits, his general condition remained stable, but the facial malformations, left esotropia, cardiac murmur and abnormal liver function persistend. The long-term outcome needed to be observed.