Leukodystrophy - paediatric

Gene: POLR1A

I don't know

Further two unrelated patients reported but overall two homozygous missense variants only.

Created: 21 Jan 2024, 6:59 a.m. | Last Modified: 21 Jan 2024, 7:02 a.m.

Panel Version: 0.304

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy, hypomyelinating, 27, MIM# 620675

Publications

• 36917474

I don't know

A different homozygous missense to the previous family, this time seen in 2 unrelated patients. Both have developmental delay, hypomyelinating leukodystrophy and cerebellar atrophy. Experiments in fibroblasts from 1 of the patients showed aberrant RNA processing and degradation. Proteomics showed abnormal protein homeostasis and ER stress responses.
The variant T642N has 15 hets 0 homs all in the European non-finnish sub pop, both patients in this study are from Europe.

Created: 6 Apr 2023, 2:18 a.m. | Last Modified: 6 Apr 2023, 2:18 a.m.

Panel Version: 0.282

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy MONDO:0019046, POLR1A related

Publications

• 36917474

Red List (low evidence)

2 brothers in a single consanguineous family with neurological disease including leukodystrophy with a homozygous variant. Reduced protein expression in patient cells.
Sources: Expert list

Created: 19 Jan 2020, 3:56 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
ataxia; psychomotor retardation; cerebellar and cerebral atrophy; leukodystrophy

Publications

• 28051070