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Expanding the phenotype of CACNA1C mutation disorders
BACKGROUND: Pathogenic variants in the L‐type Ca(2+) channel gene CACNA1C cause a multi‐system disorder that includes severe long QT syndrome (LQTS), congenital heart disease, dysmorphic facial features, syndactyly, abnormal immune function, and neuropsychiatric disorders, collectively known as Timo...
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/PMC8222832/ https://www.ncbi.nlm.nih.gov/pubmed/33797204 http://dx.doi.org/10.1002/mgg3.1673 |
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author | Gakenheimer‐Smith, Lindsey Meyers, Lindsay Lundahl, Derek Menon, Shaji C. Bunch, T. Jared Sawyer, Briana L. Tristani‐Firouzi, Martin Etheridge, Susan P. |
author_facet | Gakenheimer‐Smith, Lindsey Meyers, Lindsay Lundahl, Derek Menon, Shaji C. Bunch, T. Jared Sawyer, Briana L. Tristani‐Firouzi, Martin Etheridge, Susan P. |
author_sort | Gakenheimer‐Smith, Lindsey |
collection | PubMed |
description | BACKGROUND: Pathogenic variants in the L‐type Ca(2+) channel gene CACNA1C cause a multi‐system disorder that includes severe long QT syndrome (LQTS), congenital heart disease, dysmorphic facial features, syndactyly, abnormal immune function, and neuropsychiatric disorders, collectively known as Timothy syndrome. In 2015, a variant in CACNA1C (p.R518C) was reported to cause cardiac‐only Timothy syndrome, a genetic disorder with a mixed phenotype of congenital heart disease, hypertrophic cardiomyopathy (HCM), and LQTS that lacked extra‐cardiac features. We have identified a family harboring the p.R518C pathogenic variant with a wider spectrum of clinical manifestations. METHODS: A four‐generation family harboring the p.R518C pathogenic variant was reviewed in detail. The proband and his paternal great‐uncle underwent comprehensive cardiac gene panel testing, and his remaining family members underwent cascade testing for the p.R518C pathogenic variant. RESULTS: In addition to displaying cardinal features of CACNA1C disorders including LQTS, congenital heart disease, HCM, and sudden cardiac death, family members manifested atrial fibrillation and sick sinus syndrome. CONCLUSION: Our report expands the cardiac phenotype of CACNA1C variants and reflects the variable expressivity of mutations in the L‐type Ca(2+) channel. |
format | Online Article Text |
id | pubmed-8222832 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82228322021-06-29 Expanding the phenotype of CACNA1C mutation disorders Gakenheimer‐Smith, Lindsey Meyers, Lindsay Lundahl, Derek Menon, Shaji C. Bunch, T. Jared Sawyer, Briana L. Tristani‐Firouzi, Martin Etheridge, Susan P. Mol Genet Genomic Med Original Articles BACKGROUND: Pathogenic variants in the L‐type Ca(2+) channel gene CACNA1C cause a multi‐system disorder that includes severe long QT syndrome (LQTS), congenital heart disease, dysmorphic facial features, syndactyly, abnormal immune function, and neuropsychiatric disorders, collectively known as Timothy syndrome. In 2015, a variant in CACNA1C (p.R518C) was reported to cause cardiac‐only Timothy syndrome, a genetic disorder with a mixed phenotype of congenital heart disease, hypertrophic cardiomyopathy (HCM), and LQTS that lacked extra‐cardiac features. We have identified a family harboring the p.R518C pathogenic variant with a wider spectrum of clinical manifestations. METHODS: A four‐generation family harboring the p.R518C pathogenic variant was reviewed in detail. The proband and his paternal great‐uncle underwent comprehensive cardiac gene panel testing, and his remaining family members underwent cascade testing for the p.R518C pathogenic variant. RESULTS: In addition to displaying cardinal features of CACNA1C disorders including LQTS, congenital heart disease, HCM, and sudden cardiac death, family members manifested atrial fibrillation and sick sinus syndrome. CONCLUSION: Our report expands the cardiac phenotype of CACNA1C variants and reflects the variable expressivity of mutations in the L‐type Ca(2+) channel. John Wiley and Sons Inc. 2021-04-01 /pmc/articles/PMC8222832/ /pubmed/33797204 http://dx.doi.org/10.1002/mgg3.1673 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 | Original Articles Gakenheimer‐Smith, Lindsey Meyers, Lindsay Lundahl, Derek Menon, Shaji C. Bunch, T. Jared Sawyer, Briana L. Tristani‐Firouzi, Martin Etheridge, Susan P. Expanding the phenotype of CACNA1C mutation disorders |
title | Expanding the phenotype of CACNA1C mutation disorders |
title_full | Expanding the phenotype of CACNA1C mutation disorders |
title_fullStr | Expanding the phenotype of CACNA1C mutation disorders |
title_full_unstemmed | Expanding the phenotype of CACNA1C mutation disorders |
title_short | Expanding the phenotype of CACNA1C mutation disorders |
title_sort | expanding the phenotype of cacna1c mutation disorders |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222832/ https://www.ncbi.nlm.nih.gov/pubmed/33797204 http://dx.doi.org/10.1002/mgg3.1673 |
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