Abstract
Heterozygosity for missense variants and small in-frame deletions in GARS1 has been reported in patients with a range of genetic neuropathies including Charcot−Marie−Tooth disease type 2D (CMT2D), distal hereditary motor neuropathy type V (dHMN-V), and infantile spinal muscular atrophy (iSMA). We identified two unrelated patients who are each heterozygous for a previously unreported missense variant modifying amino-acid position 336 in the catalytic domain of GARS1. One patient was a 20-year-old woman with iSMA, and the second was a 41-year-old man with CMT2D. Functional studies using yeast complementation assays support a loss-of-function effect for both variants; however, this did not reveal variable effects that might explain the phenotypic differences. These cases expand the mutational spectrum of GARS1-related disorders and demonstrate phenotypic variability based on the specific substitution at a single residue.
Original language | English (US) |
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Pages (from-to) | 869-876 |
Number of pages | 8 |
Journal | Human mutation |
Volume | 43 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2022 |
Keywords
- Charcot−Marie−Tooth disease
- GARS1
- complementation assay
- missense variant
- spinal muscular atrophy
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)