1例新生儿血友病A的临床表型与遗传学分析

张丽亚; 闫露露; 李海波; 金夏敏; 朱丽娇; 杨挺; 陈黎丽

doi:10.16766/j.cnki.issn.1674-4152.004276

1例新生儿血友病A的临床表型与遗传学分析

doi: 10.16766/j.cnki.issn.1674-4152.004276

1.
宁波市妇女儿童医院新生儿中心，浙江宁波 315012
2.
宁波市妇女儿童医院出生缺陷中心
3.
宁波市妇女儿童医院影像中心

基金项目:

宁波市卫生健康科技计划项目 2023Y21

2024年度宁波市市级临床重点专科建设项目甬卫办医政〔2024〕93号

详细信息

通讯作者:
陈黎丽，E-mail: 532276680@qq.com

中图分类号: R554.1 R446.7
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出版历程
- 收稿日期: 2025-10-16
- 网络出版日期: 2026-01-07

Clinical phenotype and genetic analysis of a case of haemophilia A in a newborn baby

1.
Neonatal Center of Ningbo Women and Children's Hospital, Ningbo, Zhejiang 315012, China

摘要

摘要: 对1例新生儿血友病A(hemophilia A, HA)的新生儿进行遗传学分析，明确其致病原因，并进行文献复习。回顾性分析1例新生儿HA的临床表现，应用全外显子组测序(whole exome sequencing，WES)技术筛选与患儿表型相符合的致病变异，并对患儿及其母亲、同母异父姐姐进行Sanger测序验证。患儿以“帽状腱膜下血肿、头面部瘀斑、进行性血红蛋白下降”为临床表现。发现患儿凝血因子Ⅷ(coagulation factor Ⅷ, F8)基因上的1个半合移码缺失变异：c.3637del: p.I1213Ffs*5，该变异导致第1213位密码子编码的氨基酸由异亮氨酸变为苯丙氨酸，并发生移码，提前产生一个终止密码子，该变异可能导致蛋白功能异常。患儿母亲及同母异父姐姐均检出F8基因c.3637del:p.I1213Ffs*5变异，该变异可能是导致患儿发病的原因，丰富了F8基因的变异谱，并为该家系的遗传咨询和产前诊断提供了线索。
- 血友病A /
- 凝血因子Ⅷ /
- 基因变异 /
- 新生儿
Abstract: Genetic analysis was conducted on a newborn with hemophilia A (HA) to identify the cause of the disease and conduct literature review. A retrospective analysis was conducted on the clinical manifestations of a newborn with HA. Whole exome sequencing (WES) technology was used to screen for pathogenic variants that matched the child's phenotype, and Sanger sequencing was performed to validate the patient, their mother, and half siblings. The clinical manifestations of the child were "subcapsular hematoma, head and face bruising, and progressive hemoglobin decline". A hemizygous frameshift deletion mutation on the coagulation factor Ⅷ (F8) gene was discovered in the patient: c.3637del: p.I11213Ffs * 5. This mutation caused the amino acid encoded by codon 1213 to change from isoleucine to phenylalanine, resulting in a frameshift and premature production of a stop codon. This mutation might lead to abnormal protein function. The mother and half sister of the child were both found to have a c.3637del: p.I11213Ffs*5 mutation in the F8 gene, which may be the cause of the child's illness. This mutation enriches the spectrum of F8 gene mutations and provides clues for genetic counseling and prenatal diagnosis of the family.
- Haemophilia A /
- Coagulation factor Ⅷ /
- Gene variants /
- Neonates

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图 1 患儿帽状腱膜下血肿、瘀斑

Figure 1. Hematoma and petechiae beneath the capitellum in the child

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图 2 Sanger测序的结果

注：患儿及其母亲、同母异父姐姐均携带F8基因c.3637del:p.I1213Ffs*5变异，但患儿为半合移码变异，母亲、同母异父姐姐为杂合变异。

Figure 2. Results of Sanger sequencing

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