Genetic analysis of newborns with abnormal metabolism of 3-hydroxyisovalerylcarnitine.
- Author:
Dingwen WU
1
;
Bin LU
2
;
Jianbin YANG
1
;
Rulai YANG
1
;
Xinwen HUANG
1
;
Fan TONG
1
;
Jing ZHENG
1
;
Zhengyan ZHAO
1
Author Information
1. Zhejiang Neonatal Screening Center, Department of Genetics and Metabolism, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China.
2. Zhejiang Biosan Biochemical Technologies Co. Ltd, Hangzhou 310012, China.
- Publication Type:Journal Article
- MeSH:
Carbon-Carbon Ligases;
genetics;
Carnitine;
analogs & derivatives;
metabolism;
Female;
Genetic Testing;
Genetic Variation;
Humans;
Infant, Newborn;
Male;
Mutation;
Neonatal Screening;
Urea Cycle Disorders, Inborn;
genetics
- From:
Journal of Zhejiang University. Medical sciences
2019;48(4):390-396
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the genetic characterization of 3-hydroxyisovalerylcarnitine (C5-OH) metabolic abnormality in neonates.
METHODS:Fifty two newborns with increased C5-OH, C5-OH/C3 and C5-OH/C8 detected by tandem mass spectrometry during neonatal screening were enrolled in the study. Genomic DNA was extracted from the whole blood samples of 52 cases and their parents. Seventy-nine genes associated with genetic and metabolic diseases including , were targeted by liquid capture technique. Variation information of these genes was examined by high-throughput sequencing and bioinformatic analysis, and then was classified based on the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. The genetic types were classified as wild-type, -maternal-mutation, -paternal-mutation and -mutation. Wilcoxon rank-sum test was performed for the increased multiples of C5-OH calculated in neonatal screening.
RESULTS:Twenty one variants (14 novel) were identified in 37 cases, 6 variants (5 novel) in 4 cases. The increased multiple of C5-OH calculated in -maternal-mutation and -mutation groups were significantly higher than that in wild-type group (all <0.05), while there was no significant difference between MCCC1-paternal-mutation group and wild-type group (>0.05).
CONCLUSIONS:Mutations on and genes are the major genetic causes for the increased C5-OH in neonates, and maternal single heterozygous mutation can contribute to the moderately to severely increased C5-OH.
