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Progressive cerebellar atrophy in a patient with complex II and III deficiency and a novel deleterious variant in SDHA: A Counseling Conundrum
BACKGROUND: Complex II is an essential component of the electron transport chain, linking it with the tricarboxylic acid cycle. Its four subunits are encoded in the nuclear genome, and deleterious variants in these genes, including SDHA (OMIM 600857), are associated with a wide range of symptoms inc...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222855/ https://www.ncbi.nlm.nih.gov/pubmed/33960148 http://dx.doi.org/10.1002/mgg3.1692 |
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author | Sturrock, Beattie R. H. Macnamara, Ellen F. McGuire, Peter Kruk, Shannon Yang, Ivan Murphy, Jennifer Tifft, Cyndi J. Gordon‐Lipkin, Eliza |
author_facet | Sturrock, Beattie R. H. Macnamara, Ellen F. McGuire, Peter Kruk, Shannon Yang, Ivan Murphy, Jennifer Tifft, Cyndi J. Gordon‐Lipkin, Eliza |
author_sort | Sturrock, Beattie R. H. |
collection | PubMed |
description | BACKGROUND: Complex II is an essential component of the electron transport chain, linking it with the tricarboxylic acid cycle. Its four subunits are encoded in the nuclear genome, and deleterious variants in these genes, including SDHA (OMIM 600857), are associated with a wide range of symptoms including neurological disease, cardiomyopathy, and neoplasia (paraganglioma‐pheochromocytomas (PGL/PCC), and gastrointestinal stromal tumors). Deleterious variants of SDHA are most frequently associated with Leigh and Leigh‐like syndromes. METHODS AND RESULTS: Here, we describe a case of a 9‐year‐old boy with tremor, nystagmus, hypotonia, developmental delay, significant ataxia, and progressive cerebellar atrophy. He was found to have biallelic variants in SDHA, a known pathogenic variant (c.91C>T (p.R31*)), and a variant of unknown significance (c.454G>A (p.E152K)). Deficient activity of complexes II and III was detected in fibroblasts from the patient consistent with a diagnosis of a respiratory chain disorder. CONCLUSION: We, therefore, consider whether c.454G>A (p.E152K) is, indeed, a pathogenic variant, and what implications it has for family members who carry the same variant. |
format | Online Article Text |
id | pubmed-8222855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82228552021-06-29 Progressive cerebellar atrophy in a patient with complex II and III deficiency and a novel deleterious variant in SDHA: A Counseling Conundrum Sturrock, Beattie R. H. Macnamara, Ellen F. McGuire, Peter Kruk, Shannon Yang, Ivan Murphy, Jennifer Tifft, Cyndi J. Gordon‐Lipkin, Eliza Mol Genet Genomic Med Clinical Reports BACKGROUND: Complex II is an essential component of the electron transport chain, linking it with the tricarboxylic acid cycle. Its four subunits are encoded in the nuclear genome, and deleterious variants in these genes, including SDHA (OMIM 600857), are associated with a wide range of symptoms including neurological disease, cardiomyopathy, and neoplasia (paraganglioma‐pheochromocytomas (PGL/PCC), and gastrointestinal stromal tumors). Deleterious variants of SDHA are most frequently associated with Leigh and Leigh‐like syndromes. METHODS AND RESULTS: Here, we describe a case of a 9‐year‐old boy with tremor, nystagmus, hypotonia, developmental delay, significant ataxia, and progressive cerebellar atrophy. He was found to have biallelic variants in SDHA, a known pathogenic variant (c.91C>T (p.R31*)), and a variant of unknown significance (c.454G>A (p.E152K)). Deficient activity of complexes II and III was detected in fibroblasts from the patient consistent with a diagnosis of a respiratory chain disorder. CONCLUSION: We, therefore, consider whether c.454G>A (p.E152K) is, indeed, a pathogenic variant, and what implications it has for family members who carry the same variant. John Wiley and Sons Inc. 2021-05-07 /pmc/articles/PMC8222855/ /pubmed/33960148 http://dx.doi.org/10.1002/mgg3.1692 Text en © 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Clinical Reports Sturrock, Beattie R. H. Macnamara, Ellen F. McGuire, Peter Kruk, Shannon Yang, Ivan Murphy, Jennifer Tifft, Cyndi J. Gordon‐Lipkin, Eliza Progressive cerebellar atrophy in a patient with complex II and III deficiency and a novel deleterious variant in SDHA: A Counseling Conundrum |
title | Progressive cerebellar atrophy in a patient with complex II and III deficiency and a novel deleterious variant in SDHA: A Counseling Conundrum |
title_full | Progressive cerebellar atrophy in a patient with complex II and III deficiency and a novel deleterious variant in SDHA: A Counseling Conundrum |
title_fullStr | Progressive cerebellar atrophy in a patient with complex II and III deficiency and a novel deleterious variant in SDHA: A Counseling Conundrum |
title_full_unstemmed | Progressive cerebellar atrophy in a patient with complex II and III deficiency and a novel deleterious variant in SDHA: A Counseling Conundrum |
title_short | Progressive cerebellar atrophy in a patient with complex II and III deficiency and a novel deleterious variant in SDHA: A Counseling Conundrum |
title_sort | progressive cerebellar atrophy in a patient with complex ii and iii deficiency and a novel deleterious variant in sdha: a counseling conundrum |
topic | Clinical Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222855/ https://www.ncbi.nlm.nih.gov/pubmed/33960148 http://dx.doi.org/10.1002/mgg3.1692 |
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