Severe microcephaly

Gene: SARS

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 10 Oct 2023, 2:56 p.m. | Last Modified: 10 Oct 2023, 2:56 p.m.

Panel Version: 4.33

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. At least three unrelated cases with biallelic variants in this gene - microcephaly detected in all families. Although severity only reaches threshold for this panel in two families, given the extent in these cases and the consistent presentation this feature, this gene should be included on R88.

Created: 7 Mar 2023, 12:34 p.m. | Last Modified: 7 Mar 2023, 12:34 p.m.

Panel Version: 3.9

Third case identified by Bögershausen et al., 2022 (PMID: 35790048) with compound heterozygous variants in this gene, both inherited from each healthy parent. The proband displayed severe developmental delay, seizures, and severe microcephaly (HC −6.2 SD at 11 yrs old). Structural mapping showed the variant is located in the enzymes active site, likely diminishing activity, but no further functional studies were carried out.

Created: 7 Mar 2023, 12:13 p.m. | Last Modified: 7 Mar 2023, 12:13 p.m.

Panel Version: 3.8

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with microcephaly, ataxia, and seizures, OMIM:617709

Publications

• 35790048

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype. As there are only 2 cases there is not enough evidence to support a gene-disease association. This gene has been given an Amber rating.

Created: 13 Oct 2021, 1:41 p.m. | Last Modified: 13 Oct 2021, 1:41 p.m.

Panel Version: 3.1356

New gene name is SARS1

Created: 13 Oct 2021, 1:39 p.m. | Last Modified: 13 Oct 2021, 1:39 p.m.

Panel Version: 3.1355

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: 11 Oct 2021, 9:44 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability

Publications

• 28236339
• 34570399