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Fraser S, Koenig M, Farach L, et al. A De Novo case of autosomal dominant mitochondrial membrane protein-associated neurodegeneration. Mol Genet Genomic Med. 2021;9(7):e1706doi: 10.1002/mgg3.1706.
Fraser, S., Koenig, M., Farach, L., Mancias, P., & Mowrey, K. (2021). A De Novo case of autosomal dominant mitochondrial membrane protein-associated neurodegeneration. Molecular genetics & genomic medicine, 9(7), e1706. https://doi.org/10.1002/mgg3.1706
Fraser, Stuart, et al. "A De Novo case of autosomal dominant mitochondrial membrane protein-associated neurodegeneration." Molecular genetics & genomic medicine vol. 9,7 (2021): e1706. doi: https://doi.org/10.1002/mgg3.1706
Fraser S, Koenig M, Farach L, Mancias P, Mowrey K. A De Novo case of autosomal dominant mitochondrial membrane protein-associated neurodegeneration. Mol Genet Genomic Med. 2021 Jul;9(7):e1706. doi: 10.1002/mgg3.1706. Epub 2021 May 27. PMID: 34041867; PMCID: PMC8372066.
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Mol Genet Genomic Med. 2021 Jul;9(7):e1706. doi: 10.1002/mgg3.1706. Epub 2021 May 27.

A De Novo case of autosomal dominant mitochondrial membrane protein-associated neurodegeneration.

Molecular genetics & genomic medicine

Stuart Fraser, Mary Koenig, Laura Farach, Pedro Mancias, Kate Mowrey

Affiliations

  1. Department of Pediatrics, Division of Child and Adolescent Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
  2. Department of Pediatrics, Division of Medical Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.

PMID: 34041867 PMCID: PMC8372066 DOI: 10.1002/mgg3.1706

Abstract

BACKGROUND: Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a genetic neurodegenerative condition previously thought to be inherited only in an autosomal recessive pattern through biallelic pathogenic variants in C19orf12. Recent evidence has proposed that MPAN can also follow autosomal dominant forms of inheritance. We present a case of a de novo pathogenic variant in C19orf12 identified in a female with clinical features consistent with a diagnosis of MPAN, adding further evidence that the disease can be inherited in an autosomal dominant fashion.

METHODS: A 17-year-old Hispanic female was born to non-consanguineous healthy parents. She developed progressive muscle weakness and dystonia beginning when she was 12 years old. Trio, whole-exome sequencing with mitochondrial genome sequencing, and deletion/duplication analysis of both nuclear and mitochondrial genomes was performed in December 2019.

RESULTS: Whole-exome sequencing analysis revealed a single de novo variant in C19orf12. The specific variant is c.256C>T (p.Q86X) located in exon 3.

CONCLUSION: Our clinical report provides further clinical evidence that MPAN can be inherited in an autosomal dominant or recessive fashion. The patient's age of onset and clinical symptoms are very similar to the previous patient published with this specific variant as well as others with heterozygous pathogenic variants in C19orf12 in Gregory et al. 2019. Our case report highlights the importance of considering both autosomal dominant and autosomal recessive version of MPAN with all patients demonstrating clinical features suggestive of MPAN.

© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.

Keywords: brain-iron accumulation; clinical genetics; movement disorders; neurodegeneration

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