Identification of eight novel mutations and transcript analysis of two splicing mutations in Chinese newborns with MCC deficiency.
3-Methylcrotonyl-CoA carboxylase (MCC) deficiency is an autosomal recessive inborn error of leucine metabolism, caused by mutations in either MCCC1 or MCCC2 gene. We identified eight novel mutations of MCCC1 or MCCC2 in six Chinese newborns screened by tandem mass spectrometry. Transcript analysis revealed that the novel splice mutation c.639+5G>T produced a normal transcript and a transcript of exon 6 skipping which led to truncated MCCC1 protein. The remaining seven novel mutations may cause structure damage and dysfunction of MCC as predicted by in silico analysis. In conclusion, our study expands the spectrum of mutations found in MCCC1 and MCCC2 and provides a rough prevalence of 1 of 68,333 in Chinese population. Although the affected patients remained asymptomatic during follow-up, we hold the view that early detection through newborn screening, early intervention and follow-up may provide an important guidance to prevent subsequent metabolic disorders and deal with crisis later in life.
Department of Genetics and Metabolism, Children's Hospital, School of Medicine Zhejiang University, Hangzhou, China.|Department of Cell Biology and Medical Genetics, School of Medicine Zhejiang University, Hangzhou, China.
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L
Yang
Department of Genetics and Metabolism, Children's Hospital, School of Medicine Zhejiang University, Hangzhou, China.
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J
Yang
Department of Genetics and Metabolism, Children's Hospital, School of Medicine Zhejiang University, Hangzhou, China.
T
T
Zhang
Department of Cell Biology and Medical Genetics, School of Medicine Zhejiang University, Hangzhou, China.
C
C
Weng
Department of Genetics and Metabolism, Children's Hospital, School of Medicine Zhejiang University, Hangzhou, China.
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F
Hong
Department of Genetics and Metabolism, Children's Hospital, School of Medicine Zhejiang University, Hangzhou, China.
F
F
Tong
Department of Genetics and Metabolism, Children's Hospital, School of Medicine Zhejiang University, Hangzhou, China.
R
R
Yang
Department of Medicine, School of Medicine Hangzhou Normal University, Hangzhou, China.
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X
Yin
Department of Cell Biology and Medical Genetics, School of Medicine Zhejiang University, Hangzhou, China.
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P
Yu
Department of Genetics and Metabolism, Children's Hospital, School of Medicine Zhejiang University, Hangzhou, China.
X
X
Huang
Department of Cell Biology and Medical Genetics, School of Medicine Zhejiang University, Hangzhou, China.
M
M
Qi
D044466:Asian People / Q000235:genetics; D019735:Carbon-Carbon Ligases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D002675:Child, Preschool; D002681:China; D003198:Computer Simulation; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D015997:Neonatal Screening; D011487:Protein Conformation; D012326:RNA Splicing; D053719:Tandem Mass Spectrometry; D056806:Urea Cycle Disorders, Inborn / Q000235:genetics* / Q000378:metabolism
D019735:Carbon-Carbon Ligases; C021573:methylcrotonoyl-CoA carboxylase; C000609234:MCCC1 protein, human; C000609235:methylcrotonoyl-CoA carboxylase 2, human
3-methylcrotonyl-CoA carboxylase deficiency; Chinese population; mutation; newborn screening