探讨原纤维蛋白(FBN)1基因新发突变致新生儿马方综合征(MFS)的临床特征、基因检测结果和诊治方案。

选择2018年3月8日在陕西省人民医院新生儿科住院，并确诊为FBN1基因新突变致新生儿MFS的1例患儿为研究对象，确诊时年龄为生后10 h。同时，检索国内数据库中FBN1突变所致患儿发生MFS的相关文献，并进行文献复习。本研究遵循的程序符合2013年新修订的《世界医学协会赫尔辛基宣言》要求，并征得患儿监护人知情同意。

本例患儿在本院诊治结果如下。①病史采集：患儿为女性，生后即发现容貌异常、面色青紫，给予鼻导管吸氧。患儿全身皮肤干燥、松弛，双耳略大，耳位偏低，四肢细长，双上肢屈曲不能完全伸直，双腕肌力欠佳，双手呈爪状，通贯掌；双足过度跖屈。心前区听诊闻及Ⅱ～Ⅲ/6级收缩期杂音；彩色多普勒超声心动图提示动脉导管未闭，全心略大，主动脉窦部内径增宽。②基因检测结果：患儿染色体chr15-48780406位置的c.3241T>C自发杂合突变，为新发现突变，导致氨基酸改变p.Cys1081Arg(半胱氨酸>精氨酸)。该突变可能为导致本例患儿新生儿期发生MFS的缘故，但是人类基因突变数据库(HGMDpro)未见该基因突变报道。③对检索到的9篇文献中，纳入研究的9例MFS新生儿及本例患儿进行总结的结果显示，这10例患儿中，3例的基因检测均为FNB1新发基因突变，位于FBN1基因外显子24至33的突变为"新生儿区"。10例患儿临床特征均有四肢骨骼异常，8例伴心脏结构及功能异常，5例有眼部结构及功能异常，4例皮肤松弛、弹性差、皮下脂肪少，1例伴肾积水。

FBN1基因新突变位点：染色体chr15-48780406位置的c.3241T>C杂合突变。该突变可能为新生儿期MFS的新发突变类型，特别为新生儿期诊断MFS，提供了新思路。

To explore clinical features, gene detection results, diagnosis and treatment of neonatal Marfan syndrome (MFS) caused by de novo mutation of fibrinogen (FBN)1 gene.

A child who was hospitalized in the Department of Neonatology of Shaanxi Provincial People′s Hospital on March 8, 2018 and was diagnosed as neonatal MFS caused by de novo mutation of FBN1 gene, aged 10 hours after birth. At the same time, the related literatures of children with FBN1 gene mutation in domestic databases were searched and reviewed. This study was in line with the World Medical Association Declaration of Helsinki revised in 2013 and informed contents were obtained from all patients′ guardians.

① Medical history: the child was a female and was found to have an abnormal appearance and blue lips after birth, and was given oxygen by nasal cannula. The skin of the whole body was dry and flabby, the ears were slightly large, the ear position was low, the limbs were slender, the upper limbs were flexion and could not be fully straightened, the muscle strength of both wrists were poor, the hands were claw-like and palm-like. Both feet are overly toe-flexed. Grade Ⅱ-Ⅲ/6 systolic murmur could be heard in the precordial region. Color Doppler echocardiography showed patent ductus arteriosus, slightly enlarged whole heart and widened internal diameter of aortic sinus. ②Gene detection results: the heterozygous mutation of c. 3241t>C at chr15-48780406 was a de novo mutation, resulting in the change of amino acid p. Cys1081Arg (cysteine>arginine). This mutation leads to neonatal onset, and this mutation has not been reported in Human Gene Mutation Database Professional (HGMDpro). ③ Literature review results: literature review of 9 neonatal MFS cases were retrieved. Ten cases were genetically tested for de novo mutations in FNB1 gene, all of which were located in the " neonatal region" of exons 24 to 33 of the FBN1 gene. All 10 children had skeletal abnormalities of the extremities, 8 had cardiac abnormalities, 5 had ocular abnormalities, 4 had loose skin, poor elasticity, and little subcutaneous fat, and 1 had hydronephrosis.

De novo mutation site of FBN1 gene: c. 3241t>C heterozygous mutation at chromosome chr15-48780406. It provides a new idea for clinical diagnosis of MFS, especially for neonatal MFS.