Analysis of Prevalence of 3-Methylcrotonyl-CoA Carboxylase Deficiency and Mutations of MCCC1 and MCCC2 Genes in Shijiazhuang Area

doi:10.12280/gjszjk.20220495

Abstract

Abstract: Objective: To determine the prevalence of 3-methylcrotonyl-CoA carboxylase deficiency (MCCD) in neonates in Shijiazhuang City, and to test the mutations of the related genes.Methods: 185 683 neonates born in Shijiazhuang City were screened for MCCD by tandem mass spectrometry from January 2014 to December 2021, and the gene mutations of MCCC1 and MCCC2 were analyzed in those screened positive neonates. The growth and development of positive neonates were followed up. Results: Two children were diagnosed, with a prevalence of 1.08/100 000. Among them, one case was MCCD2 type with a complex heterozygous variation, which were c.592C>T and c.1144_1147delAAAAinsTTTT. The mutation of c.592C>T was a pathogenic variation while the c.1144_1147delAAAAinsTTTT was an unreported mutation, so its pathogenicity was classified as a suspected pathogenicity. The results of tandem mass spectrometry screening showed that the level of serum C5OH in the child with gene mutaion was increased. The initial screening level of C5OH was 12.26 μmol/L (normal value range is 0.07-0.61 μmol/L). The growth and development was normal during 1 year and 3 months of following up. The another child with the maternal MCCD 1 type was also tested. The primary screening level of C5OH increased to 6.28 μmol/L, and reduced to 0.75 μmol/L within the normal range after 6 months. The MCCC1 heterozygous variation was c.1679_1680insA, which was an unreported gene mutation, and the pathogenicity is classified as suspected pathogenicity. The development of this child was normal during 4 years and 3 months of following up. Conclusions: The prevalence of MCCD in neonates in Shijiazhuang area is 1.08/100 000. Three gene variation sites were found, two of which were unreported gene variations. These results enrich the variation spectrum of MCCC1 and MCCC2 genes, and provid a basis for genetic counseling.

Key words: Infant, newborn, diseases, 3-methylcrotonoyl CoA carboxylase deficiency, Prevalence, Genes, Genetic variation

JIA Li-yun, WANG Xi, MA Cui-xia, YANG Hui-xin, GONG Miao, FENG Ji-zhen. Analysis of Prevalence of 3-Methylcrotonyl-CoA Carboxylase Deficiency and Mutations of MCCC1 and MCCC2 Genes in Shijiazhuang Area[J]. Journal of International Reproductive Health/Family Planning, 2023, 42(2): 111-114.

Figures/Tables 2

References 19

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病例编号	初筛	复查	随访	参考值范围
例1	C5OH:12.26	C5OH:15.43	-	C5OH:0.07~0.61
	C0:9.89	C0:3.08		C0:7~51.4
例2	C5OH:6.28	-	C5OH:0.75	C5OH:0.07~0.61
	C0:9.44		C0:36.27	C0:7~51.4

病例编号	初筛	复查	随访	参考值范围
例1	C5OH:12.26	C5OH:15.43	-	C5OH:0.07~0.61
	C0:9.89	C0:3.08		C0:7~51.4
例2	C5OH:6.28	-	C5OH:0.75	C5OH:0.07~0.61
	C0:9.44		C0:36.27	C0:7~51.4

病例编号	基因	基因亚区	核苷酸改变	氨基酸改变	致病性评级	纯合/ 杂合	来源	相关疾病/ 遗传方式
例1	MCCC2	EX6	c.592C>T	p.Gln198^#	致病	杂合	母亲	MCCD 2型/AR
	MCCC2	EX12	c.1144_1147delAAAAinsTTTT^△	p.Lys382_Met563del insPhe	疑似致病	杂合	父亲	MCCD 2型/AR
例2	MCCC1	EX14	c.1679_1680insA	p.Asn560Lysfs*10	疑似致病	杂合	母亲	MCCD 1型/AR

病例编号	基因	基因亚区	核苷酸改变	氨基酸改变	致病性评级	纯合/ 杂合	来源	相关疾病/ 遗传方式
例1	MCCC2	EX6	c.592C>T	p.Gln198^#	致病	杂合	母亲	MCCD 2型/AR
	MCCC2	EX12	c.1144_1147delAAAAinsTTTT^△	p.Lys382_Met563del insPhe	疑似致病	杂合	父亲	MCCD 2型/AR
例2	MCCC1	EX14	c.1679_1680insA	p.Asn560Lysfs*10	疑似致病	杂合	母亲	MCCD 1型/AR