Somatic mosaicism in ALS and FTD identifies focal mutations associated with widespread degeneration

Nature Genetics 2026 Open access

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Authors: Zinan Zhou, Junho Kim, August Yue Huang, Matthew Nolan, Junseok Park, Ryan Doan, Taehwan Shin, Michael B. Miller, Mingyun Bae, Boxun Zhao, Jinhyeong Kim, Brian Chhouk
+12 more Katherine Morillo, Rebecca C. Yeh, Connor Kenny, Jennifer E. Neil, Chao-Zong Lee, Takuya Ohkubo, John Ravits, Olaf Ansorge, Lyle W. Ostrow, Clotilde Lagier‐Tourenne, Eunjung Alice Lee, Christopher A. Walsh
DOI: 10.1038/s41588-026-02570-6
Cited by: 4
References: 110

Abstract

Although mutations in many genes cause familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), most cases are sporadic (sALS and sFTD) with unclear etiology. Here we tested whether somatic mutations contribute to sALS and sFTD by deep targeted sequencing of 88 neurodegeneration-related genes in postmortem brain and spinal cord samples from 399 sporadic cases and 144 controls. Predicted deleterious somatic variants in ALS/FTD genes were observed in 2.1% of sporadic cases lacking deleterious germline variants. These variants occurred at very low allele fractions (typically

Fields of Study & Subjects

Amyotrophic Lateral Sclerosis Research Genomics and Rare Diseases Hereditary Neurological Disorders

Publication details

Journal / source
Nature Genetics
Publisher
Springer Science and Business Media LLC
Volume
58
Issue
5
Pages
1019–1029
Publication date
15 April 2026
Language
EN