Rapid screening of MMACHC gene mutations by high-resolution melting curve analysis
© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc..
BACKGROUND: Cobalamin (cbl) C is a treatable rare hereditary disorder of cbl metabolism with autosomal recessive inheritance. It is the most common organic acidemia, manifested as methylmalonic academia combined with homocysteinemia. Early screening and diagnosis are important. The mutation spectrum of the MMACHC gene causing cblC varies among populations. The mutation spectrum in Chinese population is notably different from that in other populations.
METHODS: A PCR followed by high-resolution melting curve analysis (PCR-HRM) method covering all coding exons of MMACHC gene was designed to verify 14 pathogenic MMACHC gene variants found in patients with cblC, including all common mutations in Chinese patients with cblC.
RESULT: By PCR-HRM analysis, 14 pathogenic variants of MMACHC showed distinctly different melting curves, which were consistent with Sanger sequencing. The homozygous type of the most common mutation c.609G > A (p.Trp203Ter) can also be analyzed by specially designed PCR-HRM.
CONCLUSION: The established PCR-HRM method for screening common pathogenic MMACHC variants in Chinese patients with cblC has the advantages of high accuracy, high throughput, low cost, and high speed. It is suitable for the large-sample screening of suspected children with methylmalonic acidemia and carriers in population.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Molecular genetics & genomic medicine - 8(2020), 6 vom: 04. Juni, Seite e1221 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Chao [VerfasserIn] |
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| Links: |
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| Themen: |
CblC |
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| Anmerkungen: |
Date Completed 13.04.2021 Date Revised 13.04.2021 published: Print-Electronic GENBANK: NG_013378.1, NM_015506.2 Citation Status MEDLINE |
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| doi: |
10.1002/mgg3.1221 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM307852482 |
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| 245 | 1 | 0 | |a Rapid screening of MMACHC gene mutations by high-resolution melting curve analysis |
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| 500 | |a Date Revised 13.04.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a GENBANK: NG_013378.1, NM_015506.2 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. | ||
| 520 | |a BACKGROUND: Cobalamin (cbl) C is a treatable rare hereditary disorder of cbl metabolism with autosomal recessive inheritance. It is the most common organic acidemia, manifested as methylmalonic academia combined with homocysteinemia. Early screening and diagnosis are important. The mutation spectrum of the MMACHC gene causing cblC varies among populations. The mutation spectrum in Chinese population is notably different from that in other populations | ||
| 520 | |a METHODS: A PCR followed by high-resolution melting curve analysis (PCR-HRM) method covering all coding exons of MMACHC gene was designed to verify 14 pathogenic MMACHC gene variants found in patients with cblC, including all common mutations in Chinese patients with cblC | ||
| 520 | |a RESULT: By PCR-HRM analysis, 14 pathogenic variants of MMACHC showed distinctly different melting curves, which were consistent with Sanger sequencing. The homozygous type of the most common mutation c.609G > A (p.Trp203Ter) can also be analyzed by specially designed PCR-HRM | ||
| 520 | |a CONCLUSION: The established PCR-HRM method for screening common pathogenic MMACHC variants in Chinese patients with cblC has the advantages of high accuracy, high throughput, low cost, and high speed. It is suitable for the large-sample screening of suspected children with methylmalonic acidemia and carriers in population | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a MMACHC | |
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| 650 | 4 | |a PCR-HRM | |
| 650 | 4 | |a cblC | |
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| 700 | 1 | |a Cai, Fengying |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xinjie |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Xiaowei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yani |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Qianqian |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yuqin |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Chunquan |e verfasserin |4 aut | |
| 700 | 1 | |a Shu, Jianbo |e verfasserin |4 aut | |
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