2020 年第 5 期 第 15 卷

马方综合征一家系致病基因突变筛查研究

Screening of FBN1 gene mutation in a family with Marfan′s syndrome

作者：陈丽；焦萌；金梅

英文作者：Chen Li Jiao Meng Jin Mei

单位：首都医科大学附属北京安贞医院小儿心脏中心100029

英文单位：Department of Pediatric Cardiology Beijing Anzhen Hospital Capital Medical University Beijing 100029 China

关键词：马方综合征；FBN1基因；基因突变；临床表现

英文关键词：Marfan′ssyndrome;FBN1gene;Genemutation;Clinicalmanifestation

• 摘要：

• 目的 通过对一个马方综合征家系进行FBN1基因突变筛查，探讨该家系的发病机制。方法 收集马方综合征先证者及其家系成员临床资料，采用聚合酶链反应和DNA直接测序方法 进行FBN1突变检测,确定基因突变位点。结果 先证者，女，9岁6个月，主要临床症状为累及心血管及骨骼。超声心动图表现为二尖瓣脱垂并关闭不全，主动脉窦部增宽(38.7 mm)；骨骼表现为蜘蛛指/趾，体格修长，身高158 cm，体质量41.4 kg，四肢及手指修长，手指4字征阳性，脊柱侧弯。其余家族成员临床表型正常。遗传学特点：先证者(Ⅲ:1)发现FBN1存在c.2639G>A杂合错义突变，该变异导致第880号氨基酸由Gly变为 Asp(p.Gly880Asp)，其余家族成员（Ⅰ:1, Ⅰ:2, Ⅰ:3,Ⅰ:4, Ⅱ:1, Ⅱ:2, Ⅲ:2, Ⅲ:3）上述位点为野生型。结论马方综合征家系先证者FBN1c.2639G>A(p.Gly880Asp)为新生致病性突变，此突变首次在中国马方综合征患者中发现；为此家系今后准确的遗传咨询和进一步的产前诊断提供了依据。

• Objective To identify FBN1 gene mutation in a Chinese family with Marfan′s syndrome (MFS). Methods Collect clinical data of proband of Marfan syndrome and her family members. The polymerase chain reaction and direct DNA sequencing method were used to detect FBN1 mutations to determine the gene mutation site. Results The proband was female, 9 years and 6 months old, the main clinical symptoms were involvement of blood vessels and bones. Echocardiography showed mitral valve prolapse and insufficiency, aortic sinus widening (38.7 mm); bones showed spider fingers/phalanges, slender body, height 158 cm, body weight 41.4 kg, limbs and the fingers were long, the 4 sign of the finger was positive, and the scoliosis was scoliosis. All coding exons of the FBN1 and their flanking intronic sequences were amplified by polymerase chain reaction and subjected to direct sequencing. Clinical characteristics of proband involved in cardiovascular system and skeletal system. The remains members of the family（Ⅰ:1, Ⅰ:2, Ⅰ:3, Ⅰ:4, Ⅱ:1, Ⅱ:2, Ⅲ:2, Ⅲ:3）had normal genetic characteristics. Phenotype. c.2639G>A(p.Gly880Asp)was found from proband (Ⅲ:1). Meanwhile, wild type of the above site of FBN1 was presented detected from the remains members in the family. ConclusionThe proband of the Marfan′s syndrome family was a neonatal pathogenic mutation. This mutation was identified for the first time in Chinese population Meanwhile in this Marfan′s family. This study had been provided the foundation for accurate genetic counseling and prenatal disgnosis for this family.