SF3B4基因新变异致Nager型肢面骨发育不良1型新生儿临床特征和遗传学分析

doi:10.3969/j.issn.1673-8640.2025.02.007

检验医学 ›› 2025, Vol. 40 ›› Issue (2): 142-147.DOI: 10.3969/j.issn.1673-8640.2025.02.007

• 精准医疗时代遗传性疾病基因检测专题 • 上一篇下一篇

SF3B4基因新变异致Nager型肢面骨发育不良1型新生儿临床特征和遗传学分析

王彬彬¹, 李凤启²(), 郭凤莲¹, 张蕊¹, 康慧慧², 王岳彤¹

1.周口市妇幼保健院医学遗传与产前诊断科，河南周口 466001
2.周口市妇幼保健院儿科，河南周口 466001

收稿日期:2024-05-08 修回日期:2024-11-20 出版日期:2025-02-28 发布日期:2025-03-07
通讯作者: 李凤启，E-mail：13619899785@163.com。
作者简介:王彬彬，女，1977年生，学士，主任医师，主要从事遗传性疾病产前诊断工作。

Clinical characteristic and genetic analysis of a new mutation of SF3B4 gene causing neonatal acrofacial dysostosis 1，Nager type

WANG Binbin¹, LI Fengqi²(), GUO Fenglian¹, ZHANG Rui¹, KANG Huihui², WANG Yuetong¹

1. Department of Medical Genetics and Prenatal Diagnosis，Zhoukou Maternal and Child Health Hospital，Zhoukou 466001，Henan，China
2. Department of Pediatrics，Zhoukou Maternal and Child Health Hospital，Zhoukou 466001，Henan，China

Received:2024-05-08 Revised:2024-11-20 Online:2025-02-28 Published:2025-03-07

摘要/Abstract

摘要：

目的探讨1例Nager型肢面骨发育不良1型（AFD1）新生儿的临床特征和遗传学病因。方法对患儿及其父母行家系全外显子组测序，并采用Sanger测序验证。采用生物信息学方法分析基因变异的生物危害性。构建变异质粒，分析变异蛋白的表达情况。结果患儿出生时即表现为特殊面容（眼睑下斜、上睑下垂、耳位偏低和下颌骨发育不良），并伴有新生儿呼吸衰竭和酸中毒。基因检测结果显示患儿SF3B4基因发生移码突变c.980dup（p.G328Rfs*158），其父母均为野生型。检索公共变异数据库（dbSNP数据库、千人基因组数据库和ExAC数据库），未见SF3B4 c.980dup（p.G328Rfs*158）被收录。检索Pubmed和HGMD数据库，未见相应变异的报道，属SF3B4基因新变异。与野生型相比，变异蛋白几乎不表达，SF3B4 c.980dup（p.G328Rfs*158）变异可能导致蛋白降解。结论 AFD1患儿的临床表型可能是由SF3B4 c.980dup（p.G328Rfs*158）变异导致的。对于有下颌骨发育不良等面容特征的患儿应及早进行分子诊断。

关键词: SF3B4基因, Nager型肢面骨发育不良1型, 分子诊断

Abstract:

Objective To investigate the clinical characteristics and genetic etiology of a neonatal acrofacial dysostosis 1，Nager type. Methods Trio-whole-exome sequencing was performed on the patient and her parents，and Sanger sequencing was used for verification. Bioinformatics was used to analyze the pathogenicity of variation. Mutant plasmids were constructed in vitro to observe protein overexpression levels. Results The neonate exhibited distinctive facial appearance at birth，which included downslanting eyelids，ptosis，low-set ears and mandibular hypoplasia，accompanied by neonatal respiratory failure and acidosis. Genetic testing results revealed a frameshift variation in SF3B4 gene，c.980dup（p.G328Rfs*158），which was not present in the parents. The variation was not found in public variation database（dbSNP，1000 Genomes and ExAC）. A search of PubMed and HGMD databases revealed no previous reports of the variation，indicating it is a new variation in SF3B4. The mutated protein was almost not expressed compared to wild-type，indicating that the mutated protein may be degraded caused by SF3B4 c.980dup（p.G328Rfs*158）. Conclusions The clinical characteristics of the patient may be caused by SF3B4 c.980dup（p.G328Rfs*158）. Early molecular diagnosis should be made for children with distinctive facial appearance such as mandibular hypoplasia.

Key words: SF3B4 gene, Acrofacial dysostosis 1, Nager type, Molecular diagnosis

中图分类号:

R446.7

王彬彬, 李凤启, 郭凤莲, 张蕊, 康慧慧, 王岳彤. SF3B4基因新变异致Nager型肢面骨发育不良1型新生儿临床特征和遗传学分析[J]. 检验医学, 2025, 40(2): 142-147.

WANG Binbin, LI Fengqi, GUO Fenglian, ZHANG Rui, KANG Huihui, WANG Yuetong. Clinical characteristic and genetic analysis of a new mutation of SF3B4 gene causing neonatal acrofacial dysostosis 1，Nager type[J]. Laboratory Medicine, 2025, 40(2): 142-147.

图/表 3

图1 患儿面容特征注：特殊面容，表现为眼睑下斜、上睑下垂、耳位偏低、颧骨扁平、下颌骨发育不良。

图2 患儿及其父母Sanger测序分析注：患儿SF3B4基因发生移码突变c.980dupG（p.Gln328Argfs*158）（红色箭头）；其父母均正常。

图3 体外功能实验注：（a）SF3B4蛋白序列示意图（Uniprot ID：Q15427），主要包括N端2个RNA识别基序（RNA recognition motif，RRM）和1个C端脯氨酸富集（Prolin-residues，PR）结构域，c.980dupG（p.Gln328Argfs*158）位于PR结构域中；（b）蛋白免疫印迹电泳图；（c）野生型组、变异型组和对照组SF3B4蛋白表达比较。

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SF3B4基因新变异致Nager型肢面骨发育不良1型新生儿临床特征和遗传学分析

Clinical characteristic and genetic analysis of a new mutation of SF3B4 gene causing neonatal acrofacial dysostosis 1，Nager type

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