Early onset or syndromic epilepsy

Gene: PPT1

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 neuronal ceroid lipofuscinosis 1 (CLN1). Classic infantile onset, seizures have been reported along with other features of this metabolic disease. Vesa et al, 1995 - hom mutation R122W in patients dfrom 40/42 Finnsh CLN1 families - founder effect. Mitchison et al, 1998 - hom or compound het in 11 patients with CLN1. Das et al, 1998, 19 diff mutations in 57 of 58 mutated alleles from 29 patient derived cell lines. R151* 40% of alleles and T75P 13% of alleles. Functional work done on some variants.

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
Ceroid lipofuscinosis neuronal, 256730

Publications

• 11717424

Comment when marking as ready: Sufficient cases

Created: 4 Dec 2018, 10:34 p.m.

Comment on list classification: Numerous variants and cases presenting with seizures.

Created: 4 Dec 2018, 10:30 p.m.

Associated with Ceroid lipofuscinosis, neuronal, 1 in OMIM and Gene2Phenotype.

PMID: 7637805 (Vesa et al. 1995) - identified a homozygous mutation (R122W) in the PPT1 gene in patients with infantile-onset CLN1 from 40 of 42 Finnish families. The findings were consistent with a founder effect. The parents were carriers. Clinical phenotypes of patients are not given.

PMID: 9425237 (Mitchison et al. 1998) - homozygosity or compound heterozygosity for mutations in the PPT1 gene in 10 families with juvenile-onset CLN1. 5 mutations observed and in all cases followed a Mendelian pattern of inheritance. Epilepsy was observed in patients from 7 families, with onset from the age of 7.

PMID: 9664077 (Das et al. 1998) reports 19 different mutations in the PPT1 gene 29 patient-derived cell lines. 8 patients presented with seizures.

Created: 4 Dec 2018, 10:30 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this metabolic disorder.

Created: 19 Aug 2018, 11:33 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ceroid lipofuscinosis, neuronal, 1, MIM#256730

Variants in this GENE are reported as part of current diagnostic practice

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

"PPT" was submitted by an expert, which is most likely to be this HGNC-approved symbol.

Created: 1 Jul 2015, 3:16 p.m.