Severe microcephaly

Gene: NARS

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 10 Mar 2022, 10:52 a.m. | Last Modified: 10 Mar 2022, 10:52 a.m.

Panel Version: 2.282

Green List (high evidence)

Added new-gene-name tag, new approved HGNC gene symbol for NARS is NARS1

Created: 9 Dec 2020, 2:33 p.m. | Last Modified: 9 Dec 2020, 2:33 p.m.

Panel Version: 2.53

Comment on list classification: There is sufficient evidence to rate this gene Green at the next GMS panel update (added 'for-review' tag)

Created: 9 Dec 2020, 2:33 p.m. | Last Modified: 9 Dec 2020, 2:33 p.m.

Panel Version: 2.53

Associated with relevant phenotype in OMIM, and in Gene2Phenotype with 'confirmed' disease confidence for 'NARS1 Neurodevelopmental Disorder (monoallelic)' and 'probable' for 'NARS1 Neurodevelopmental Disorder (biallelic)'

Total of 24 patients from 13 unrelated families with biallelic variants in the NARS1 gene (PMIDs: 32738225 and 32788587) and 8 unrelated patients with de novo heterozygous variants (PMIDs: 32738225). Microcephaly was observed in the majority of cases (90%), with severity relevant to this panel (≥ 3 SD). These cases predominantly presented with primary microcephaly; however, secondary microcephaly was also noted. Other features include GDD/ID, seizures, ataxia, and dysmorphism. Supportive functional data.
Sources: Literature

Created: 9 Dec 2020, 2:33 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive, OMIM:619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, autosomal dominant, OMIM:619092

Publications

• 32738225
• 32788587