FGG基因c.1073C>A突变致新生儿先天性纤维蛋白原缺乏症临床分析并文献复习  

Congenital afibrinogenemia in neonate caused by FGG gene c.1073C>A mutation:a case report and literature review

作　　者：孙梦雅[1] 刘燕[1] 秦苗[1] 姜红[1] Sun Mengya;Liu Yan;Qin Miao;Jiang Hong(Department of Neonatology,Affiliated Hospital of Qingdao University,Qingdao 266000,Shandong Province,China)

机构地区：[1]青岛大学附属医院新生儿科,青岛266000

出　　处：《中华妇幼临床医学杂志（电子版）》2022年第3期323-329,共7页Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)

基　　金：山东省自然科学基金青年项目(ZR2020QH054)。

摘　　要：目的探讨编码纤维蛋白原(Fg)γ多肽链基因-FGG突变,所致新生儿先天性纤维蛋白原缺乏症(CA)的临床及遗传学特点。方法选择2021年5月,青岛大学附属医院新生儿科诊治的1例CA新生儿为研究对象,回顾性分析其临床病例资料。采用单基因病高通量测序技术,检测本例患儿外周血FGG基因,患儿父母进行特定基因位点的Sanger法测序,以明确患儿基因突变来源。对中国知网数据库、万方数据知识服务平台及PubMed数据库中,关于新生儿期起病的FGG基因突变所致CA病例进行检索,总结CA新生儿的临床及遗传学特点。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。监护人对患儿的诊治知情同意,并签署临床研究知情同意书。结果①临床资料:本例患儿系女性,生后11.7 h时,因"发现面部淤斑4 h"入院,无发热,不伴其他部位出血等。除面部淤斑外,体格检查无异常。入院时凝血常规检查结果异常,主要为抗凝血酶Ⅲ与血浆Fg含量均较正常值低,分别为31.0%与0.18 g/L;凝血酶原时间与凝血酶时间均较正常值延长,分别为22.3 s与24.0 s。同时,患儿母亲于分娩前发现血浆Fg减少(为0.52 g/L),不伴出血症状。②本例患儿及其母亲外周血检出FGG(4q28|NM_000509.4)基因exon 8:c.1073C>A p.(Ser358Tyr)错义突变、杂合突变,患儿该突变来自其母亲。该突变位点在人类基因变异数据库(HGMD)等基因库中目前未见收录,亦未见文献报道,生物信息学软件预测其有致病可能。③经静脉输注冷沉淀治疗后,患儿症状好转出院,出院诊断为新生儿CA,低出生体重儿。对本例患儿随访至5个月龄,无出血表现。④文献检索结果:仅发现3例新生儿期起病的FGG基因突变所致CA患儿。其中,患儿1、2(患儿1缺乏详细描述,患儿2为女性,诊断时为10 d龄)为FGG基因缺失/移码突变(均为纯合子)所致CA,FGG基因突变分别为g.194delA、c.1096delObjective To investigate clinical and genetic characteristics of neonatal congenital afibrinogenemia(CA)caused by FGG gene mutation encoding fibrinogen(Fg)γ polypeptide chain.Methods A baby girl with CA diagnosed and treated in Neonatology Department of Affiliated Hospital of Qingdao University in May 2021 was selected into this study.Clinical data of this girl were analyzed retrospectively.The FGG gene in peripheral blood of this neonate was detected by high-throughput sequencing of monogenic disease.Sanger sequencing of specific gene loci was performed on the parents of this neonate to identify the source of her gene mutation.The CA newborns caused by FGG gene mutation onset in neonatal period in China National Knowledge Infrastructure database,Wanfang database and PubMed database were searched,and the clinical and genetic characteristics of CA newborns were summarized.The procedure followed in this study was consistent with the requirement of Helsinki Declaration of World Medical Association revised in 2013.The guardian informed consent to the diagnosis and treatment of the infant,and signed the informed consent form of research.Results①At 11.7 h after birth,this neonate(female)was admitted to hospital because of"facial ecchymosis for 4 h"without bleeding in other parts of body and fever.Except facial ecchymosis,the rest of physical examination was normal.The abnormal results of routine coagulation examination at admission were mainly of antithrombin Ⅲ and plasma Fg level were lower than those normal reference parameters,which were 31.0% and 0.18 g/L,respectively;prothrombin time and thrombin time were longer than those normal reference parameters,which were 22.3 s and 24.0 s,respectively;meanwhile,plasma Fg level of her mother was also lower than normal(0.52 g/L)before giving birth,and without bleeding symptoms.②FGG(4q28|NM_000509.4)gene exon 8:c.1073C>A p.(Ser358Tyr)missense mutation and heterozygous mutation were detected in peripheral blood of FGG of this neonate and her mother.The mutation of FGG o

关 键 词：纤维蛋白原缺乏血症 先天性 纤维蛋白原 FGG基因 突变 误义 出血 婴儿 新生 

分 类 号：R722.1[医药卫生—儿科]