先天性糖基化障碍Ⅰq型患儿基因检测结果分析和文献回顾

doi:10.3969/j.issn.1673-8640.2023.02.007

摘要/Abstract

摘要：

目的对1例先天性糖基化障碍（CDG）-Ⅰq型患儿的临床特征和遗传学特点进行分析，并进行文献回顾。方法收集1例CDG-Ⅰq型患儿临床资料，对患儿及其父母进行全外显子组家系测序（Trio-WES）。对筛选出的变异位点进行生物信息学分析，并采用Sanger测序进行验证。检索同类病例报道文献，总结CDG-Ⅰq型患儿临床和遗传学特征。结果患儿主要表现为发育迟缓伴特殊面容，头颅磁共振成像提示脑外间隙增宽。Trio-WES检测结果提示患儿SRD5A3基因存在复合杂合变异[NM_024592.5：c.411G>A（p.Trp137Ter）和c.208_c.209insA（p.Asp70Glufs*150）]，该变异dbSNP数据库、千人基因组数据库和ExAC数据库均未收录，ClinVar和HGMD数据库也未见该变异位点相关报道。共检索到国内外报道的34例CDG-Ⅰq型患儿的详细临床信息，主要临床特征为发育迟缓、眼部疾病、皮肤病和其他表型，SRD5A3基因变异类型主要为无义变异和移码变异。结论报道的CDG-Ⅰq型患儿为SRD5A3基因新发变异所致，丰富了SRD5A3基因变异谱。Trio-WES有助于CDG-Ⅰq型的精准诊断。

关键词: SRD5A3基因, 全外显子组家系测序, 先天性糖基化障碍

Abstract:

Objective The clinical and genetic characteristics of a child with congenital glycosylation disorder（CDG） -Ⅰq have been analyzed，and the literature has been reviewed. Methods The clinical data of a child with CDG-Ⅰq were collected and analyzed，and the trio-whole-exome sequencing（Trio-WES） was performed on the child and her parents. Bioinformatics analysis was carried out on the screened mutations，and Sanger sequencing was used to verify. The reports of similar cases were searched，and the clinical and genetic characteristics of the children with CDG-Ⅰq were reviewed. Results The main manifestation of the child was developmental retardation with special facial features，and brain magnetic resonance imaging showed that the extracerebral space was widened. The results of trio-WES showed that the SRD5A3 of the child had a compound heterozygous mutation [NM_024592.5：c.411G>A（ p.Trp137Ter） and c.208_c.209insA（ p.Asp70Glufs*150）]，and the mutation was not included in the dbSNP database，1000 Genomes database and ExAC database. The ClinVar and HGMD databases also did not see the report of the mutation. Literature review collected detailed clinical information of 34 children with CDG-Ⅰq reported. The main clinical features were developmental retardation，eye disease，dermatosis and other phenotypes. The main types of SRD5A3 mutations were nonsense mutations and frameshift mutations. Conclusions A case of CDG-Ⅰq caused by novel mutation of SRD5A3 has been reported，which enriches the variation spectrum of SRD5A3. Trio-WES is helpful for the accurate diagnosis of CDG-Ⅰq.

Key words: SRD5A3 gene, Trio-whole-exome sequencing, Congenital glycosylation disorder

中图分类号:

R446.1

张智香, 田恒峰, 衡二虎. 先天性糖基化障碍Ⅰq型患儿基因检测结果分析和文献回顾[J]. 检验医学, 2023, 38(2): 137-142.

ZHANG Zhixiang, TIAN Hengfeng, HENG Erhu. Genetic test and literature review in a child with congenital glycosylation disorder type Ⅰq[J]. Laboratory Medicine, 2023, 38(2): 137-142.

图/表 4

参考文献 19

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病例序号	文献	发病年龄	性别	碱基变异位点	氨基酸变异位点	特殊面容	发育迟缓	肌张力低	共济失调或刻板行为	癫痫	脑结构异常	眼病	皮肤表现
1	[2]	4个月	女	c.603G>A	p.Trp201*	+	+	+	+	+	+	+	+
2	[2]	4岁	男	c.603G>A	p.Trp201*	+	+	+	+	+	+	+	+
3	[2]	3个月	男	c.57G>A	p.Trp19*	+	+	+	+	+	-	+	-
4	[2]	9个月	女	c.562+3delG / c.921C>G	p.Pro307Arg	+	+	+	+	-	-	+	-
5	[2]	/	女	c.562+3delG / c.921C>G	p.Pro307Arg	+	+	+	-	-	-	+	-
6	[3]	5个月	男	c.57G>A	p.Trp19*	+	+	-	-	+	-	+	+
7	[7]	/	/	c.286_288 delins	p.Gln96delinsX	/	+	+	+	+	-	+	/
8	[7]	/	/	c.286_288 delins	p.Gln96delinsX	/	+	-	+	-	+	+	/
9	[7]	/	/	c.286_288 delins	p.Gln96delinsX	/	+	+	+	+	+	+	/
10	[7]	/	/	c.286_288 delins	p.Gln96delinsX	/	+	-	+	-	-	+	/
11	[7]	/	/	c.292_293del	p.Leu98ValfsX121	/	+	+	+	+	+	+	/
12	[7]	/	/	c.292_293del	p.Leu98ValfsX121	/	+	+	+	-	/	+	/
13	[7]	/	/	c.320G>A	p.Trp107*	/	+	+	-	+	+	+	/
14	[7]	/	/	c.489C>A	p.Tyr163*	/	+	+	+	-	-	+	/
15	[7]	/	/	c.424C>T	p.Arg142*	/	/	/	/	/	/	/	/
16	[7]	/	/	c.29C>A	p.Ser10*	/	+	+	+	-	-	+	/
17	[7]	/	/	c.57G>A	p.Trp19*	/	+	+	/	-	+	+	/
18	[7]	/	/	染色体重排		/	+	+	+	-	+	+	/
19	[7]	/	/	c.57G>A	p.Trp19*	/	+	+	+	+	-	+	/
20	[8]	3.5岁	男	c.530e531del	p.Val177Alafsx42	-	+	+	-	-	+	+	+
21	[9]	4个月	男	c.57G>A	p.Trp19*	-	+	-	-	+	-	-	-
22	[10]	4个月	男	c.320G>A	p.Trp107*	+	+	+	-	+	-	+	+
23	[11]	8岁	女	c.57G>A	p.Trp19*	+	+	/	/	/	+	+	+
24	[12]	/	女	c.286_288 delins	p.Gln96delinsX	-	+	-	-	-	-	+	+
25	[13]	9个月	男	c.943C>T	p.Pro315Ser	-	+	+	-	-	+	+	+
26	[13]	/	男	c.943C>T	p.Pro315Ser	-	+	+	+	-	+	+	+
27	[13]	18个月	女	c.57G>A	p.Trp19*	-	+	+	+	-	/	+	-
28	[13]	/	女	c.57G>A	p.Trp19*	-	+	+	-	-	/	+	+
29	[13]	2个月	女	c.57G>A	p.Trp19*	-	+	+	+	-	+	+	-
30	[13]	6个月	男	c.57G>A	p.Trp19*	-	+	+	+	-	+	+	-
31	[13]	6周	女	c.57G>A	p.Trp19*	-	+	+	+	-	/	+	+
32	[13]	3周	女	c.57G>A	p.Trp19*	-	+	+	-	-	/	+	+
33	[13]	6周	男	c.57G>A	p.Trp19*	-	+	+	-	-	+	+	-
34	[13]	出生	女	c.286_288 delins	p.Gln96delinsX	+	+	+	-	-	+	+	+
35	[13]	出生	男	c.286_288 delins	p.Gln96delinsX	+	+	+	-	-	+	+	+
36	本例	2个月	女	c.411G>A、	p.Trp137Ter、	+	+	+	-	-	+	+	+
				c.208_c.209insA	p.Asp70Glufs*150

病例序号	文献	发病年龄	性别	碱基变异位点	氨基酸变异位点	特殊面容	发育迟缓	肌张力低	共济失调或刻板行为	癫痫	脑结构异常	眼病	皮肤表现
1	[2]	4个月	女	c.603G>A	p.Trp201*	+	+	+	+	+	+	+	+
2	[2]	4岁	男	c.603G>A	p.Trp201*	+	+	+	+	+	+	+	+
3	[2]	3个月	男	c.57G>A	p.Trp19*	+	+	+	+	+	-	+	-
4	[2]	9个月	女	c.562+3delG / c.921C>G	p.Pro307Arg	+	+	+	+	-	-	+	-
5	[2]	/	女	c.562+3delG / c.921C>G	p.Pro307Arg	+	+	+	-	-	-	+	-
6	[3]	5个月	男	c.57G>A	p.Trp19*	+	+	-	-	+	-	+	+
7	[7]	/	/	c.286_288 delins	p.Gln96delinsX	/	+	+	+	+	-	+	/
8	[7]	/	/	c.286_288 delins	p.Gln96delinsX	/	+	-	+	-	+	+	/
9	[7]	/	/	c.286_288 delins	p.Gln96delinsX	/	+	+	+	+	+	+	/
10	[7]	/	/	c.286_288 delins	p.Gln96delinsX	/	+	-	+	-	-	+	/
11	[7]	/	/	c.292_293del	p.Leu98ValfsX121	/	+	+	+	+	+	+	/
12	[7]	/	/	c.292_293del	p.Leu98ValfsX121	/	+	+	+	-	/	+	/
13	[7]	/	/	c.320G>A	p.Trp107*	/	+	+	-	+	+	+	/
14	[7]	/	/	c.489C>A	p.Tyr163*	/	+	+	+	-	-	+	/
15	[7]	/	/	c.424C>T	p.Arg142*	/	/	/	/	/	/	/	/
16	[7]	/	/	c.29C>A	p.Ser10*	/	+	+	+	-	-	+	/
17	[7]	/	/	c.57G>A	p.Trp19*	/	+	+	/	-	+	+	/
18	[7]	/	/	染色体重排		/	+	+	+	-	+	+	/
19	[7]	/	/	c.57G>A	p.Trp19*	/	+	+	+	+	-	+	/
20	[8]	3.5岁	男	c.530e531del	p.Val177Alafsx42	-	+	+	-	-	+	+	+
21	[9]	4个月	男	c.57G>A	p.Trp19*	-	+	-	-	+	-	-	-
22	[10]	4个月	男	c.320G>A	p.Trp107*	+	+	+	-	+	-	+	+
23	[11]	8岁	女	c.57G>A	p.Trp19*	+	+	/	/	/	+	+	+
24	[12]	/	女	c.286_288 delins	p.Gln96delinsX	-	+	-	-	-	-	+	+
25	[13]	9个月	男	c.943C>T	p.Pro315Ser	-	+	+	-	-	+	+	+
26	[13]	/	男	c.943C>T	p.Pro315Ser	-	+	+	+	-	+	+	+
27	[13]	18个月	女	c.57G>A	p.Trp19*	-	+	+	+	-	/	+	-
28	[13]	/	女	c.57G>A	p.Trp19*	-	+	+	-	-	/	+	+
29	[13]	2个月	女	c.57G>A	p.Trp19*	-	+	+	+	-	+	+	-
30	[13]	6个月	男	c.57G>A	p.Trp19*	-	+	+	+	-	+	+	-
31	[13]	6周	女	c.57G>A	p.Trp19*	-	+	+	+	-	/	+	+
32	[13]	3周	女	c.57G>A	p.Trp19*	-	+	+	-	-	/	+	+
33	[13]	6周	男	c.57G>A	p.Trp19*	-	+	+	-	-	+	+	-
34	[13]	出生	女	c.286_288 delins	p.Gln96delinsX	+	+	+	-	-	+	+	+
35	[13]	出生	男	c.286_288 delins	p.Gln96delinsX	+	+	+	-	-	+	+	+
36	本例	2个月	女	c.411G>A、	p.Trp137Ter、	+	+	+	-	-	+	+	+
				c.208_c.209insA	p.Asp70Glufs*150