Genetic analysis of neonates with abnormal isovaleryl carnitine metabolism
10.3760/cma.j.cn101070-20221102-01248
- VernacularTitle:异戊酰基肉碱代谢异常新生儿的遗传学分析
- Author:
Dingwen WU
1
;
Rulai YANG
;
Chen LIU
;
Fan TONG
;
Shuai CHEN
;
Zhengyan ZHAO
Author Information
1. 浙江大学医学院附属儿童医院遗传与代谢科，国家儿童健康与疾病临床医学研究中心，浙江省新生儿疾病诊治重点实验室，杭州 310052
- Keywords:
Isovaleryl carnitine;
Genetic testing;
Gene variation;
Neonatal screening
- From:
Chinese Journal of Applied Clinical Pediatrics
2023;38(1):49-53
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic causes of abnormal isovaleryl carnitine (C5) metabolism in newborns.Methods:Retrospective study.The screening and clinical follow-up data of 34 neonates with elevated C5 levels shown by the tandem mass spectrometry test in Children′s Hospital, Zhejiang University School of Medicine from January 2018 to December 2021 were collected.Afterwards, their ethylenediaminetetraacetic acid (EDTA) anticoagulant venous blood was collected to extract genomic DNA.A total of 79 genes related to genetic metabolic diseases, such as ACADSB, IVD and ACADM, were captured by liquid-phase capture technology.High-throughput sequencing and bioinformatics analysis were used to acquire gene variation information and the genes were categorized by American College of Medical Genetics and Genomics classification standard.According to the results of genetic analysis, the newborns with C5 elevation were divided into 3 groups: non-mutation group(11 cases), ACADSB mutation group(16 cases) and IVD mutation group(7 cases). Wilcoxon rank sum test was performed to analyze the difference between these groups. Results:Among 34 neonates, 6 ACADSB variants were detected in 16 cases, and 2 of them [c.461G>A (p.G154E), c.746delC(p.P249Lfs*15)] were novel variants.Eleven IVD variants were detected in 7 cases, and 7 of them [c.118A>G(p.N40D), c.296-10C>G, c.302A>G(p.Y101C), c.537G>A(p.M179I), c.667C>T(p.R223W), c.983A>G(p.K328R), c.1147+ 5G>A] were never reported before.There was no significant difference in the C5 concentration in initial screening among the three groups ( P>0.05). Conclusions:Mutations in ACADSB and IVD genes are the main causes of augmented C5 levels in neonatal screening.For newly discovered genetic variants, functional prediction by multiple bioinformatics analysis software is recommended.And it is also important to carry out clinical follow-up and evaluation.
