Genetic Epilepsy

Gene: PRPF8

Green List (high evidence)

PMID 35543142 O'Grady et al 2022 report 14 unrelated individuals with heterozygous PRPF8 variants and ID, dev delay, dymorphic features and epilepsy (7/14). Short stature, abnormal gait and cardiac anomalies also reported. 11 variants identified were de novo, 1 variant - maternal mosaicism, 1 variant - duo sequencing (not identified in mother, father could not be sequenced). 1 individual did not have parental testing. Cardiac anomalies varied and included benign cardiac tumour, dilated cardiomyopathy, dilated aortic root (COL5A2 VUS also identified), bicuspid aortic valve, cardiac arrest, self-resolving ASD/VSD.

Heterozygous PRPF8 variants previously associated with retinitis pigmentosa. 1 out of the 14 individuals in this cohort had a diagnosis of RP. RP variants noted to cluster in the C'terminal MPN domain. The individual with RP in this paper had a variant in the preceding RNAase H homology domain near the C-terminus. Not all of the individuals in this paper had formal ophthalmological examination.
Sources: Literature

Created: 2 Jun 2022, 1:43 a.m. | Last Modified: 2 Jun 2022, 1:48 a.m.

Panel Version: 0.1612

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epilepsy; intellectual disability; Retinitis pigmentosa 13 - MIM#600059

Publications

• 35543142

Comment on phenotypes: Established Retinitis pigmentosa gene.
PMID: 33057194 - Has been identified as a gene with significant de novo enrichment in a large trio study from the Deciphering Developmental Disorders study. 29 de novo variants (2 frameshift, 19 missense, 1 stopgain, 7 synonymous) identified in ~10,000 cases with developmental disorders (no other phenotype info provided).

Created: 3 Nov 2020, 12:15 a.m. | Last Modified: 3 Nov 2020, 12:15 a.m.

Panel Version: 0.5295