Mackenzie's Mission_Reproductive Carrier Screening

Gene: SNORD118

Red List (low evidence)

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.

Not suitable for inclusion on carrier screening panel.

Created: 9 Jun 2021, 4:08 a.m. | Last Modified: 9 Jun 2021, 4:08 a.m.

Panel Version: 0.102

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Publications

• 32361877
• 33029936