Perspectives on the genomics of HSP beyond Mendelian inheritance
- 1Hussman Institute for Human Genomics, University of Miami, United States
- 2Dr. John T. Macdonald Foundation Department of Human Genetics, Leonard M. Miller School of Medicine, United States
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.
Keywords: HEREDIT SPASTIC PARAPLEGIA, Genomics, Risk allele, Mendelian, Non-Mendelian inheritance
Received: 05 Aug 2018;
Accepted: 25 Oct 2018.
Edited by:Toshitaka Kawarai, Tokushima University, Japan
Copyright: © 2018 Bis-Brewer and Zuchner. 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.
* Correspondence: Dr. Stephan Zuchner, Hussman Institute for Human Genomics, University of Miami, Coral Gables, FL 33136, Florida, United States, SZuchner@med.miami.edu