Hereditary Neuropathy_CMT - isolated

Gene: SARS

Comment when marking as ready: potentially specific to the aminoacylation domain

Created: 6 Oct 2022, 3:52 a.m. | Last Modified: 6 Oct 2022, 3:52 a.m.

Panel Version: 1.19

Green List (high evidence)

-Two missense variants within the aminoacylation domain identified in 16 affected individuals from 3 distinct CMT families
-Mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2α phosphorylation
Sources: Literature

Created: 6 Oct 2022, 3:31 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Genetic peripheral neuropathy MONDO#0020127, SARS1-related

Publications

• 36088542

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

3rd family identified.

note that the gene is also known as SARS1

Created: 4 Aug 2022, 7:01 a.m. | Last Modified: 4 Aug 2022, 7:01 a.m.

Panel Version: 1.220

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder MONDO#070009, SARS1-related

Publications

• 35790048

Variants in this GENE are reported as part of current diagnostic practice

I don't know

Summary - 2 unrelated families with overlapping ID phenotype, and supporting in vitro and patient cell assays.
PMID: 28236339 - an Iranian family (distantly related) segregating a homozygous missense (c.514G>A, p.Asp172Asn) with moderate ID, microcephaly, ataxia, speech impairment, and aggressive behaviour. Also, supporting in vitro functional assays demonstrating altered protein function.
PMID: 34570399 - a consanguineous Turkish family segregating a homozygous missense (c.638G>T, p.(Arg213Leu)) with developmental delay, central deafness, cardiomyopathy, and metabolic decompensation during fever leading to death. Also, reduced protein level and enzymatic activity in patient cells.
Sources: Literature

Created: 4 Oct 2021, 4:04 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability

Publications

• 28236339
• 34570399