Pathogenic missense variants altering codon 336 of GARS1 lead to divergent dominant phenotypes.
Hum Mutat
; 43(7): 869-876, 2022 07.
Article
in En
| MEDLINE
| ID: mdl-35332613
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Charcot-Marie-Tooth Disease
/
Glycine-tRNA Ligase
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Hum Mutat
Journal subject:
GENETICA MEDICA
Year:
2022
Document type:
Article
Affiliation country:
United States