Genetic test and literature review in a child with congenital glycosylation disorder type Ⅰq

doi:10.3969/j.issn.1673-8640.2023.02.007

Abstract

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

CLC Number:

R446.1

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.

Figures/Tables 4

References 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