,
1
,
2
and
1,
*
娟 骆
四川大学华西第二医院 新生儿科 出生缺陷与相关妇儿疾病教育部重点实验室 (成都 610041),
Department of Neonatology, West China Second University Hospital, Key Laboratory of Birth Defects and Related Disease of Women and Children of the Ministry of Education, Sichuan University, Chengdu 610041, China
苏容 段
四川大学华西第二医院 新生儿科 出生缺陷与相关妇儿疾病教育部重点实验室 (成都 610041),
Department of Neonatology, West China Second University Hospital, Key Laboratory of Birth Defects and Related Disease of Women and Children of the Ministry of Education, Sichuan University, Chengdu 610041, China
华 王
四川大学华西第二医院 新生儿科 出生缺陷与相关妇儿疾病教育部重点实验室 (成都 610041),
Department of Neonatology, West China Second University Hospital, Key Laboratory of Birth Defects and Related Disease of Women and Children of the Ministry of Education, Sichuan University, Chengdu 610041, China
四川大学华西第二医院 新生儿科 出生缺陷与相关妇儿疾病教育部重点实验室 (成都 610041),
Department of Neonatology, West China Second University Hospital, Key Laboratory of Birth Defects and Related Disease of Women and Children of the Ministry of Education, Sichuan University, Chengdu 610041, China
滨州医学院第一临床医学系 (滨州 264003),
First School of Clinical Medicine, Bingzhou Medical University, Binzhou 264003, China
结论
CD主要依据基因检测进行确诊,其治疗特点为精准个体化原则,对于没有临床表现的患者无需特殊治疗,但对备孕的女性患者充分做好产前诊断及随访十分重要,避免流产及产后凝血功能异常所致的并发症出现。
Keywords:
纤维蛋白原, 遗传性异常纤维蛋白原血症, 家系, 基因突变, 产前诊断, 遗传咨询
Abstract
Objective
To improve the understanding and diagnosis and treatment of congenital dysfibrinogenemia (CD) through analyzing the clinical data of a pediatric patient and his pedigree.
Methods
The clinical manifestations, laboratory findings and treatment of a case of CD diagnosed at West China Second University Hospital, Sichuan University and those of its pedigree members were analyzed, and genetic tracing and follow-up were conducted on the patient and its pedigree.
Results
The child has no clinical manifestations at the time of admission. Coagulation function examination showed normal prothrombin time (PT), normal activated partial thrombin time (APTT), significantly prolonged thrombin time (TT), fibrinogen activity (Fg: C<0.5 g/L) measured with the Clauss method, and fibrinogen antigen (Fg: Ag) measured at 2.8 g/L with PT algorithm. Gene sequencing results showed that heterozygous missense mutation c.901C>T (p.Arg301Cys) in exon 8 of
FGG
gene. Combined with the family history, the child was diagnosed with CD. During the follow-up of 4
+
months, the patient did not present bleeding, abnormal coagulation or thrombosis, and the coagulation function did not show significant changes compared with the findings obtained on admission.
Conclusion
The diagnosis of CD is confirmed mainly based on genetic testing and the treatment is characterized by the principle of precise individualized treatment. No special treatment is needed for patients presenting no clinical manifestations. However, it is important to provide thorough prenatal diagnosis and follow-up services for female patients planning for pregnancy so as to prevent miscarriage and complications caused by postpartum coagulation dysfunction.
Keywords:
Fibrinogen, Congenital dysfibrinogenemia, Pedigree, Genetic mutation, Prenatal diagnosis, Genetic counseling
遗传性异常纤维蛋白原血症(congenital dysfibrinogenemia, CD)是一种因基因突变而导致纤维蛋白原(fibrinogen, Fg)分子结构和功能异常的遗传性疾病,大多数为常染色体显性遗传,小部分为隐性遗传。其临床表现具有高度异质性,患者中约55%无症状、25%有出血症状、20%有血栓形成,其中部分患者可同时或先后有出血和血栓形成
[
1
]
,部分患者表现为伤口愈合不良,合并妊娠的女性CD患者可出现反复流产及胎盘早剥并可致产后出血及血栓形成的风险升高
[
2
]
。本文收集了1例CD患儿及其家系资料,报道如下。
1. 病例资料
患儿,男,系G
12
P
3
、胎龄37
+1
周足月新生儿,因胎膜早破剖宫产娩出,否认宫内窘迫史及生后抢救史,体格检查无异常。凝血功能:凝血酶原时间(PT)16.3 s,活化的部分凝血活酶时间(APTT)38.4 s,凝血酶时间(TT)38.1 s,Clauss法检测纤维蛋白原活性(fibrinogen activity, Fg: C)<0.5 g/L,PT演算法测定纤维蛋白原抗原(fibrinogen antigen, Fg: Ag)2.8 g/L,Fg: Ag/Fg: C>5.6。因患儿母亲已确诊为CD患者,故提取患儿外周血DNA对纤维蛋白原编码基因
FGA
、
FGB
和
FGG
的所有外显子及侧翼序列和启动子区进行PCR扩增后(
FGG-
exon8引物F: 5′-GAAGCATCCTACGAAAGAGGG-3′; R: 5′-ACTGTGGGTTGTGGGATCTC-3′)采用Sanger法测序分析,结果为
FGG
基因第8号外显子杂合性错义变异c.901C>T(p.Arg301Cys)(
)。诊断为CD,因无出血及血栓形成等表现,未予特殊治疗,嘱密切观察病情变化,出院后血液科长期随访。
Articles from
Journal of Sichuan University (Medical Sciences)
are provided here courtesy of
Editorial Board of Journal of Sichuan University (Medical Sciences)