Tandem Mass Spectrometry Screening and Gene Mutation Analysis of Neonatal Hyperprolinemia

doi:10.12280/gjszjk.20210433

Abstract

Abstract:

Objective: To retrospectively analyze the screening status of neonatal hyperprolinemia in Shijiazhuang City, so as to understand its prevalence and proline dehydrogenase (PRODH) mutations. Methods: Tandem mass spectrometry technology-non-derivatization method was used to detect proline levels in dried blood spots on filter paper. Live birth newborns born between January 2014 and December 2020 in Shijiazhuang City were screened. Genetic sequencing technology was further used to detect the mutations of the PRODH gene in children with positive screening. Sanger sequencing was used for verification. Results: Ten of the 172 895 newborns were screened suspected positive, 5 cases were genetically confirmed, with the incidence rate 1/34 579. Among the 5 children, 4 cases were compound heterozygous mutations in PRODH gene, 1 case was loss of heterozygous gene overall. Gene mutation analysis revealed four kinds of point mutations, in which two mutations, c.1322T>C and c.1363G>T, have been reported. Two mutations, c.273+1G>C and c.334delA, were not yet reported. Conclusions: The prevalence of neonatal hyperprolinemia in Shijiazhuang City was 1/34 579. Five cases of children were diagnosed with gene mutations, and two unreported gene mutations were found, which enriched the gene database.

Key words: Neonatal screening, Tandem mass spectrometry, Hyperprolinemia, Genes, Mutation

FENG Lu-lu, JIA Li-yun, GONG Miao, MA Cui-xia, FENG Ji-zhen. Tandem Mass Spectrometry Screening and Gene Mutation Analysis of Neonatal Hyperprolinemia[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(1): 18-21.

Figures/Tables 4

References 22

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病例	性别	初筛	召回复查
1	女	573.16	428.34
2	女	331.82	-
3	男	91.19	349.72
4	男	853.55	400.70
5	女	568.35	766.65
6	女	399.24	518.31
7	女	409.01	737.56
8	女	424.60	638.73
9	男	616.01	509.46
10	男	560.06	720.50

病例	性别	初筛	召回复查
1	女	573.16	428.34
2	女	331.82	-
3	男	91.19	349.72
4	男	853.55	400.70
5	女	568.35	766.65
6	女	399.24	518.31
7	女	409.01	737.56
8	女	424.60	638.73
9	男	616.01	509.46
10	男	560.06	720.50

病例	基因	转录本	Exon/Intron	核苷酸	氨基酸	杂合/纯合	突变来源
1	PRODH	NM_016335	Exon12	c.1322T>C	p.L441P	杂合	父亲
		NM_016335	Intron2	c.273+1G>C^☆	p.?	杂合	母亲
2	PRODH	NM_016335	Exon3	c.334delA^☆	p.T112Pfs*7	杂合	父亲
		NM_016335	Exon12	c.1322T>C	p.L441P	杂合	母亲
3	PRODH	基因整体杂合缺失
4	PRODH	NM_016335	Exon12	c.1322T>C	p.L441P	杂合	母亲
		NM_016335	Exon12	c.1363G>T	p.A455S	杂合	父亲
5	PRODH	NM_016335	Exon12	c.1363G>T	p.A455S	杂合	父亲
		NM_016335	Exon12	c.1322T>C	p.L441P	杂合	母亲

病例	基因	转录本	Exon/Intron	核苷酸	氨基酸	杂合/纯合	突变来源
1	PRODH	NM_016335	Exon12	c.1322T>C	p.L441P	杂合	父亲
		NM_016335	Intron2	c.273+1G>C^☆	p.?	杂合	母亲
2	PRODH	NM_016335	Exon3	c.334delA^☆	p.T112Pfs*7	杂合	父亲
		NM_016335	Exon12	c.1322T>C	p.L441P	杂合	母亲
3	PRODH	基因整体杂合缺失
4	PRODH	NM_016335	Exon12	c.1322T>C	p.L441P	杂合	母亲
		NM_016335	Exon12	c.1363G>T	p.A455S	杂合	父亲
5	PRODH	NM_016335	Exon12	c.1363G>T	p.A455S	杂合	父亲
		NM_016335	Exon12	c.1322T>C	p.L441P	杂合	母亲

病例	随访截止时年龄	饮食治疗	药物治疗	随访截止时脯氨酸浓度（μmol/L）	生长发育情况
1	5岁7个月	6个月	无	805	正常
2	4岁2个月	无	无	426	正常
3	3岁6个月	无	无	457	正常
4	3岁10个月	3个月	无	639	正常
5	1岁5个月	无	无	4 200	语言稍落后