Prepair 1000+

Gene: SNORD118

Red List (low evidence)

Review by MM team: SNORD118 is a small nucleolar RNA required for ribosomal RNA processing. Biallelic variants in SNORD118 have been reported in association with leukoencephalopathy with calcifications and cysts (LCC), in more than 60 patients from more than 50 unrelated families.

It is difficult (?impossible) to predict the severity/age of onset from the genotype. In a comprehensive case series, Crow et al. 2021 report 64 individuals with age of onset varying from 3 weeks to 67 years with disease onset after 40 years in 12.5% of patients. They describe no obvious genotype-phenotype correlation that could explain this variability in age of onset. Cullinane et al 2020 describe a sibling pair with the same homozygous variant – one severely affected and the other with mild clinical features at 35yo.

There is some doubt on a population frequency basis about pathogenicity of some of the variants reported in Crow et al, and as there is no separate way of assessing pathogenicity of variants in an RNA gene, variant curation for the gene is likely to be challenging even for previously reported variants.

Created: 20 Jul 2022, 3:09 a.m. | Last Modified: 20 Jul 2022, 3:09 a.m.

Panel Version: 0.52

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukoencephalopathy, brain calcifications, and cysts, MIM#614561

Publications

• 32361877
• 33029936

I don't know

Well-established gene disease association however the phenotype can be highly variable. No obvious genotype-phenotype correlation.

Gene removed from the latest version of the Mackenzie's Mission gene panel. Sufficient coverage over this gene and confident that if a previously reported variant will be reliably detected

Created: 19 Jul 2022, 4:45 a.m. | Last Modified: 19 Jul 2022, 4:45 a.m.

Panel Version: 0.50

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukoencephalopathy, brain calcifications, and cysts (MIM#614561)

Publications

• 33029936