Analysis of gene mutations of medium-chain acyl-coenzyme a dehydrogenase deficiency (MCADD) by next-generation sequencing in Henan, China.
Clin Chim Acta
; 536: 155-161, 2022 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-36096209
ABSTRACT
BACKGROUND:
Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) is a rare inherited metabolic disorder of fatty acid ß-oxidation and one of the most common inborn errors of metabolism. The incidence of MCADD varies among regions and ethnic groups. To date, few cases of MCADD have been documented in China.OBJECTIVE:
The present study aimed to find out the novel genetic pathogenic variants in the Chinese patients and evaluate the detection rate of the disease of high-frequency ACADM pathogenic variants in different regions of China.METHODS:
6 cases of MCADD were screened by tandem mass spectrometric (MS/MS) among 245 054 newborns. We performed next-generation sequencing on 6 families of infants with MCADD. We used the REVEL method to predict the protein function of the detected missense variants and used SPDBV 4.10 to predict the protein 3D structure model. We identified pathogenic variants of ACADM gene in 6 cases of MCADD, and then assessed these variants through Sanger sequencing and association analysis.RESULTS:
The incidence of neonatal MCADD was 1/40,842 in Henan province. Among the 6 patients, five cases were compound heterozygous variants, one case was homozygous variants. DNA sequencing revealed 4 known (c.449_452del, c.1085G > A, c.1229 T > C, c.589A > G) and 3 novel mutations (c.849 + 5_849 + 8del, c.427A > G, c.1181C > T) in the ACADM gene. Mutation c.1085G > A (p.G362E) was most frequent among Henan people and shows obvious differences between North and South of China.CONCLUSION:
MCADD is relatively rare in China, and c.1085G > A (p.G362E) is a common mutation in Henan population. Our findings, especially novel variants, will help improve the understanding of the genetic background and have facilitated clinical diagnosis and genetic counseling for the affected families.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espectrometria de Massas em Tandem
/
Erros Inatos do Metabolismo Lipídico
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
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Infant
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Newborn
Idioma:
En
Revista:
Clin Chim Acta
Ano de publicação:
2022
Tipo de documento:
Article