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Mutation analysis, treatment and prenatal diagnosis of Chinese cases of methylmalonic acidemia

Methylmalonic acidemia (MMA)-affected patients may have developmental, hematological, neurological, metabolic, ophthalmological, and dermatological clinically abnormal findings. This study aimed to identify mutations in 13 Chinese MMA cases. We provided genetic counseling, treatment, and prenatal di...

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Autores principales: Zhang, Chuan, Wang, Xing, Hao, Shengju, Zhang, Qinghua, Zheng, Lei, Zhou, Bingbo, Liu, Furong, Feng, Xuan, Chen, Xue, Ma, Panpan, Chen, Cuixia, Cao, Zongfu, Ma, Xu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385101/
https://www.ncbi.nlm.nih.gov/pubmed/32719376
http://dx.doi.org/10.1038/s41598-020-69565-z
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author Zhang, Chuan
Wang, Xing
Hao, Shengju
Zhang, Qinghua
Zheng, Lei
Zhou, Bingbo
Liu, Furong
Feng, Xuan
Chen, Xue
Ma, Panpan
Chen, Cuixia
Cao, Zongfu
Ma, Xu
author_facet Zhang, Chuan
Wang, Xing
Hao, Shengju
Zhang, Qinghua
Zheng, Lei
Zhou, Bingbo
Liu, Furong
Feng, Xuan
Chen, Xue
Ma, Panpan
Chen, Cuixia
Cao, Zongfu
Ma, Xu
author_sort Zhang, Chuan
collection PubMed
description Methylmalonic acidemia (MMA)-affected patients may have developmental, hematological, neurological, metabolic, ophthalmological, and dermatological clinically abnormal findings. This study aimed to identify mutations in 13 Chinese MMA cases. We provided genetic counseling, treatment, and prenatal diagnosis for the families with MMA. Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was performed and the results were confirmed by gas chromatography and mass spectrometry (GC/MS). Variant screening in probands was performed by targeted next-generation sequencing. Identified variants were confirmed by Sanger sequencing. Of these 13 MMA cases, seven were isolated MMA, and among them, six were caused by variants in MMUT and one was caused by a variant in MCEE. The other six cases were MMA with homocystinuria, which was caused by variants in MMACHC. We found six novel variants in three MMA-causing genes as follows: c.2008G>A, c.301_302insTA, c.984delC, and c.319A>T of MMUT; c.445T>C of MMACHC; and c.296T>C of MCEE. We provided prenatal diagnosis for two families with MMA at their next pregnancy, and one family had a healthy newborn. In conclusion, our findings expand the spectrum of genotypes in MMA. Effective genetic counseling is required to allow awareness of the patients’ families that MMA disease is treatable and a good prognosis can be obtained.
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spelling pubmed-73851012020-07-28 Mutation analysis, treatment and prenatal diagnosis of Chinese cases of methylmalonic acidemia Zhang, Chuan Wang, Xing Hao, Shengju Zhang, Qinghua Zheng, Lei Zhou, Bingbo Liu, Furong Feng, Xuan Chen, Xue Ma, Panpan Chen, Cuixia Cao, Zongfu Ma, Xu Sci Rep Article Methylmalonic acidemia (MMA)-affected patients may have developmental, hematological, neurological, metabolic, ophthalmological, and dermatological clinically abnormal findings. This study aimed to identify mutations in 13 Chinese MMA cases. We provided genetic counseling, treatment, and prenatal diagnosis for the families with MMA. Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was performed and the results were confirmed by gas chromatography and mass spectrometry (GC/MS). Variant screening in probands was performed by targeted next-generation sequencing. Identified variants were confirmed by Sanger sequencing. Of these 13 MMA cases, seven were isolated MMA, and among them, six were caused by variants in MMUT and one was caused by a variant in MCEE. The other six cases were MMA with homocystinuria, which was caused by variants in MMACHC. We found six novel variants in three MMA-causing genes as follows: c.2008G>A, c.301_302insTA, c.984delC, and c.319A>T of MMUT; c.445T>C of MMACHC; and c.296T>C of MCEE. We provided prenatal diagnosis for two families with MMA at their next pregnancy, and one family had a healthy newborn. In conclusion, our findings expand the spectrum of genotypes in MMA. Effective genetic counseling is required to allow awareness of the patients’ families that MMA disease is treatable and a good prognosis can be obtained. Nature Publishing Group UK 2020-07-27 /pmc/articles/PMC7385101/ /pubmed/32719376 http://dx.doi.org/10.1038/s41598-020-69565-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Chuan
Wang, Xing
Hao, Shengju
Zhang, Qinghua
Zheng, Lei
Zhou, Bingbo
Liu, Furong
Feng, Xuan
Chen, Xue
Ma, Panpan
Chen, Cuixia
Cao, Zongfu
Ma, Xu
Mutation analysis, treatment and prenatal diagnosis of Chinese cases of methylmalonic acidemia
title Mutation analysis, treatment and prenatal diagnosis of Chinese cases of methylmalonic acidemia
title_full Mutation analysis, treatment and prenatal diagnosis of Chinese cases of methylmalonic acidemia
title_fullStr Mutation analysis, treatment and prenatal diagnosis of Chinese cases of methylmalonic acidemia
title_full_unstemmed Mutation analysis, treatment and prenatal diagnosis of Chinese cases of methylmalonic acidemia
title_short Mutation analysis, treatment and prenatal diagnosis of Chinese cases of methylmalonic acidemia
title_sort mutation analysis, treatment and prenatal diagnosis of chinese cases of methylmalonic acidemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385101/
https://www.ncbi.nlm.nih.gov/pubmed/32719376
http://dx.doi.org/10.1038/s41598-020-69565-z
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