Early onset or syndromic epilepsy

Gene: DPYD

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Green List (high evidence)

AR dihydropyrimidine dehydrogenase defic and 5-fluorouracil toxicity. Large phenotypic variability ranging from no symptoms to a convulsive disorder with motor and mental retardation in hom patients. Van Gennip et al, 1994 and Meinsma et al, 1995 - splicing variant (IVS14+1G>A)- parents and an unaff sib het carriers. vreken et al, 1997 - 4bp del in 2 aff sibs of a Dutch consang family - both aff had seizures. Van Kuilenburg et al, 1999 - 22 patients from 17 families with complete DPD defic - 7 diff mutations identified - 52% of mutant alleles is splice variant reported by Meinsma et al. Van Kuilenberg et al, 2009 - intragenic deletions of the DPYD defic in whom no point mutations identified. 3 had a hom 13.8kb del and 1 had a hom 122kb del. All patients born of consang families. 5th patient compound het for a 4bp del and a 14-Mb del on the chromosome. All patients severely aff incl epilepsy.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
5-fluorouracil toxicity,274270; Dihydropyrimidine dehydrogenase deficiency,274270

Publications

• 28275972
• 19296131

Green List (high evidence)

Associated with phenotype in OMIM, not in G2P. At least 5 variants reported. Pharmacogentic tag added with comment: Heterozygous individuals can be affected by fluorouracil toxicity.

Created: 16 Mar 2017, 2:08 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
5-fluorouracil toxicity 274270; Dihydropyrimidine dehydrogenase deficiency 274270