Novel Pathogenic Variants in <i>POLR3K</i> Cause POLR3-Related Leukodystrophy.

ABSTRACT: POLR3-related hypomyelinating leukodystrophy (POLR3-HLD) is a rare inherited neurological disorder caused by biallelic pathogenic variants in specific genes encoding subunits of RNA polymerase III (Pol III). Here, we report the third patient worldwide with pathogenic variants in POLR3K and clinical features consistent with POLR3-HLD. The female patient presented with mild intellectual and behavioural disturbances in childhood, as well as growth delay, with brain MRI revealing diffuse hypomyelination and a pattern consistent with POLR3-HLD. In adolescence, she manifested minor motor dysfunction. Next-generation sequencing revealed a paternally inherited missense variant in POLR3K (c.322G>T; p.D108Y) and a maternally inherited large deletion, spanning approximately 17.8 kb from

SUBMITTER: Perrier S 

PROVIDER: S-EPMC11919171 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature