14例原发性纤毛运动障碍临床表现、纤毛结构及基因特点分析

doi:10.12372/jcp.2025.25e0254

摘要/Abstract

摘要：

目的探讨原发性纤毛运动障碍（PCD）临床表现、纤毛结构及基因变异特点。方法回顾性分析2017年1月至2024年12月在医院经支气管镜黏膜活检电镜检查或二代测序全外显子组基因检测确诊为PCD患儿的临床资料。结果共纳入14例患儿，男4例、女10例，中位发病年龄6.3（1.3~7.9）岁，中位诊断年龄8.0（7.0 ~10.8）岁。主要临床表现包括慢性湿性咳嗽（14例，100%），鼻/鼻窦炎（12例，85.7%），支气管扩张及肺不张（9例，64.3%），内脏转位（3例，21.4%），慢性中耳炎（2例，14.3%）。14例患儿支气管镜下均表现为化脓性支气管炎（100%），2例镜下合并支气管狭窄，1例合并支气管闭塞。10例患儿在急性感染控制至少2周后检测鼻呼出一氧化氮（nNO），8例nNO均明显降低，2例nNO>77 nL/min。7例患儿进行全外显子组检测，其中2例阴性，5例检出双等位基因变异，DNAH5基因2例，CCNO基因2例，DNAH1基因1例。结论 PCD临床表型以慢性咳嗽、鼻窦炎、支气管扩张为主，内脏转位及新生儿期呼吸窘迫发生率低，部分患儿nNO高于阳性阈值，并发支气管闭塞，主要基因变异为DNAH5和CCNO。

关键词: 原发性纤毛运动障碍, 纤毛超微结构, 基因变异, 儿童

Abstract:

Objective To explore the clinical manifestations, ciliary structure and genetic variation characteristics of primary ciliary dyskinesia (PCD). Methods A retrospective analysis of the clinical data of children diagnosed with primary ciliary dyskinesia (PCD) by bronchoscopic mucosal biopsy electron microscopy or whole exome sequencing (WES) from January 2017 to December 2024 at the hospital. Results A total of 14 children (4 boys and 10 girls) were included, the median age of onset was 6.3 (1.3-7.9) years, and the median age of diagnosis was 8.0 (7.0-10.8) years. The main clinical manifestations included chronic wet cough (14 cases, 100%), rhinosinusitis (12 cases, 85.7%), bronchiectasis and atelectasis (9 cases, 64.3%), situs inversus (3 cases, 21.4%), and chronic otitis media (2 cases, 14.3%). All 14 children presented with bronchoscopic findings of purulent bronchitis (100%), 2 patients were combined with bronchial stenosis, and 1 was combined with bronchial occlusion under bronchoscopy. Nasal exhaled nitric oxide (nNO) was detected in 10 children at least 2 weeks after the acute infection was controlled. nNO was significantly decreased in 8 cases, and nNO was > 77 nL/min in 2 cases. Seven children underwent exome sequencing. Among them, 2 children were negative and 5 were detected with biallelic variations (2 cases of DNAH5 gene variation, 2 cases of CCNO gene variation, and 1 case of DNAH1 gene variation). Conclusions The clinical phenotypes of PCD are mainly chronic cough, sinusitis, and bronchiectasis, with low incidence of situs inversus and neonatal respiratory distress. Some children have nNO levels above the positive threshold and may develop bronchial obstruction. The main gene variations are DNAH5 and CCNO.

Key words: primary ciliary dyskinesia, ciliary ultrastructure, gene variation, child

中图分类号:

张未, 汪洋, 邓文华, 吴亚斌. 14例原发性纤毛运动障碍临床表现、纤毛结构及基因特点分析[J]. 临床儿科杂志, 2025, 43(9): 680-685.

ZHANG Wei, WANG Yang, DENG Wenhua, WU Yabin. Analysis of clinical manifestations, ciliary structure and genetic characteristics of primary ciliary dyskinesia in 14 children[J]. Journal of Clinical Pediatrics, 2025, 43(9): 680-685.

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参考文献 26

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患儿	性别	诊断年龄	起病年龄	NRD	慢性咳嗽	鼻窦炎	中耳炎	内脏转位	肺不张	支气管扩张	镜下表现	nNO/ nL·min^-1	TEM纤毛超微结构	TEM纤毛缺陷分类
例1	女	8.0岁	6.5岁	无	有	有	无	无	有	有	右中叶狭窄，支气管化脓征	365.4	IDA，部分ODA及微管数量异常	Ⅰ类
例2	女	7.0岁	6.0岁	无	有	有	无	有	有	无	支气管化脓征	8.4	ODA+部分IDA、微管数量异常	Ⅰ类
例3	男	11.0岁	7.0岁	无	有	有	无	无	有	有	支气管化脓征	21	未做	未做
例4	女	0.2岁	3d	有	有	无	无	无	有	无	支气管化脓征	未做	未做	未做
例5	女	7.0岁	2.0岁	有	有	有	无	无	有	无	支气管化脓征，支气管闭塞	15	未做	未做
例6	女	15.0岁	1.0岁	有	有	有	有	有	有	有	支气管化脓征	4.8	未做	未做
例7	女	11.0岁	10.0岁	无	有	有	无	无	有	有	支气管化脓症	26.4	ODA+IDA	Ⅰ类
例8	女	10.0岁	9.0岁	无	有	有	无	无	无	有	支气管化脓征	10.8	ODA+IDA	Ⅰ类
例9	女	12.0岁	11.0岁	无	有	无	无	无	无	有	支气管化脓征，左上叶狭窄	22.8	双联纤毛/CP，外周微管缺失或增多	Ⅱ类
例10	女	10.0岁	8.0岁	无	有	有	无	无	无	有	支气管化脓征	142.8	ODA+IDA，部分微管数量异常	Ⅰ类
例11	男	8.0岁	7.5岁	无	有	有	无	无	无	无	支气管化脓征	22.2	ODA+IDA	Ⅰ类
例12	女	3.0岁	2.0岁	无	有	有	无	无	有	有	支气管化脓征	未做	ODA+IDA	Ⅰ类
例13	男	1.0岁	0.8岁	无	有	有	无	无	无	无	支气管化脓征	未做	ODA	Ⅰ类
例14	男	8.0岁	0.1岁	有	有	有	有	有	有	有	支气管化脓征	未做	CP/ODA	Ⅰ+Ⅱ类

患儿	基因	核苷酸改变	外显子/ 内含子	遗传方式	来源	ACMG证据	变异评级	变异类型	变异状态	氨基酸改变
例1	DNAH1	c.2650C>T	exon16	AR	父亲	PM1+PM2+PP3	VUS	错义突变	复合杂合	p.Arg884Trp
例1	DNAH1	c.10084G>A	exon64	AR	母亲	PM1+PM2+PP3	VUS	错义突变	复合杂合	p.Val3362Met
例2	DNAH5	c.1320+1G>A	IVS10	AR	母亲	PVS1+PM2	LP	剪接突变	复合杂合	p.?
例2	DNAH5	c.13510A>T	exon78	AR	父亲	PVS1+PM2+PM3	P	无义突变	复合杂合	p.Lys4504Ter
例3	DNAH5	c.5563_5564insA	exon34	AR	父亲	PVS1+PM2+PM3 _Strong	P	移码突变	复合杂合	p.Ile1855fsTer6
例3	DNAH5	c.4147_4148delAinsTCC	exon27	AR	母亲	PVS1+PM2+PM3	P	移码突变	复合杂合	p.Ile1383fsTer22
例4	CCNO	c.258_262dup	exon1	AR	父亲	PVS1+PM3+PP1	P	移码突变	纯合	p.Gln88ArgfsTer8
例4	CCNO	c.258_262dup	exon1	AR	母亲	PVS1+PM3+PP1	P	移码突变	纯合	p.Gln88ArgfsTer8
例5	CCNO	c.317A>C	exon1	AR	父亲	PM2+PM3+PP3+PP4	VUS	错义突变	复合杂合	p.Tyr106ser
例5	CCNO	c.253_262dup	exon1	AR	母亲	PVS1+PM2+PP1	P	移码突变	复合杂合	p.Gin88ArgfsTer51
例6	DNAH5	c.8569G>T	exon51	AR	－	PVS1+PM2	LP	无义突变	杂合	p.Glu2857Ter