Impaired Function of a Rare Mutation in the MMUT Gene Causes Methylmalonic Acidemia in a Chinese Patient

Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disorder mainly caused by mutations in the methylmalonyl coenzyme A mutase (MCM) gene (MMUT) and leads to the reduced activity of MCM. In this study, a 3-year-old girl was diagnosed with carnitine deficiency secondary to methylmalonic...

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Bibliographic Details
Main Authors: Siyu Dai, Yanting Yang, Yaqian Li, Hongqian Liu
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Genetics Research
Online Access:http://dx.doi.org/10.1155/2022/5611697
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Summary:Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disorder mainly caused by mutations in the methylmalonyl coenzyme A mutase (MCM) gene (MMUT) and leads to the reduced activity of MCM. In this study, a 3-year-old girl was diagnosed with carnitine deficiency secondary to methylmalonic acidemia by tandem mass spectrometry (MS/MS) and gas chromatography/mass spectrometry (GS/MS). Whole-exome sequencing (WES) was performed on the patient and identified two compound heterozygous mutations in MMUT: c.554C>T (p. S185F) and c.729–730insTT (p. D244Lfs∗39). Bioinformatics analysis predicted that the rare missense mutation of c.554C>T would be damaging. Moreover, this rare mutation resulted in the reduced levels of MMUT mRNA and MMUT protein. Collectively, our findings provide a greater understanding of the effects of MMUT variants and will facilitate the diagnosis and treatment of patients with MMA.
ISSN:1469-5073