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Perspectives on the Genomics of HSP Beyond Mendelian Inheritance

Hereditary Spastic Paraplegia is an extraordinarily heterogeneous disease caused by over 50 Mendelian genes. Recent applications of next-generation sequencing, large scale data analysis, and data sharing/matchmaking, have discovered a quickly expanding set of additional HSP genes. Since most recentl...

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Autores principales: Bis-Brewer, Dana M., Züchner, Stephan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275194/
https://www.ncbi.nlm.nih.gov/pubmed/30534106
http://dx.doi.org/10.3389/fneur.2018.00958
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author Bis-Brewer, Dana M.
Züchner, Stephan
author_facet Bis-Brewer, Dana M.
Züchner, Stephan
author_sort Bis-Brewer, Dana M.
collection PubMed
description Hereditary Spastic Paraplegia is an extraordinarily heterogeneous disease caused by over 50 Mendelian genes. Recent applications of next-generation sequencing, large scale data analysis, and data sharing/matchmaking, have discovered a quickly expanding set of additional HSP genes. Since most recently discovered HSP genes are rare causes of the disease, there is a growing concern of a persisting diagnostic gap, estimated at 30–40%, and even higher for sporadic cases. This missing heritability may not be fully closed by classic Mendelian mutations in protein coding genes. Here we show strategies and published examples of broadening areas of attention for Mendelian and non-Mendelian causes of HSP. We suggest a more inclusive perspective on the potential final architecture of HSP genomics. Efforts to narrow the heritability gap will ultimately lead to more precise and comprehensive genetic diagnoses, which is the starting point for emerging, highly specific gene therapies.
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spelling pubmed-62751942018-12-10 Perspectives on the Genomics of HSP Beyond Mendelian Inheritance Bis-Brewer, Dana M. Züchner, Stephan Front Neurol Neurology Hereditary Spastic Paraplegia is an extraordinarily heterogeneous disease caused by over 50 Mendelian genes. Recent applications of next-generation sequencing, large scale data analysis, and data sharing/matchmaking, have discovered a quickly expanding set of additional HSP genes. Since most recently discovered HSP genes are rare causes of the disease, there is a growing concern of a persisting diagnostic gap, estimated at 30–40%, and even higher for sporadic cases. This missing heritability may not be fully closed by classic Mendelian mutations in protein coding genes. Here we show strategies and published examples of broadening areas of attention for Mendelian and non-Mendelian causes of HSP. We suggest a more inclusive perspective on the potential final architecture of HSP genomics. Efforts to narrow the heritability gap will ultimately lead to more precise and comprehensive genetic diagnoses, which is the starting point for emerging, highly specific gene therapies. Frontiers Media S.A. 2018-11-26 /pmc/articles/PMC6275194/ /pubmed/30534106 http://dx.doi.org/10.3389/fneur.2018.00958 Text en Copyright © 2018 Bis-Brewer and Züchner. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Bis-Brewer, Dana M.
Züchner, Stephan
Perspectives on the Genomics of HSP Beyond Mendelian Inheritance
title Perspectives on the Genomics of HSP Beyond Mendelian Inheritance
title_full Perspectives on the Genomics of HSP Beyond Mendelian Inheritance
title_fullStr Perspectives on the Genomics of HSP Beyond Mendelian Inheritance
title_full_unstemmed Perspectives on the Genomics of HSP Beyond Mendelian Inheritance
title_short Perspectives on the Genomics of HSP Beyond Mendelian Inheritance
title_sort perspectives on the genomics of hsp beyond mendelian inheritance
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275194/
https://www.ncbi.nlm.nih.gov/pubmed/30534106
http://dx.doi.org/10.3389/fneur.2018.00958
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