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Genetic epilepsy syndromes

Gene: PCDH12

Green List (high evidence)

PCDH12 (protocadherin 12)
EnsemblGeneIds (GRCh38): ENSG00000113555
EnsemblGeneIds (GRCh37): ENSG00000113555
OMIM: 605622, Gene2Phenotype
PCDH12 is in 11 panels

6 reviews

Rebecca Foulger (Genomics England curator)

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

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

AR MISSBC - progressive microcephaly, early-onset seizures, spasticity and brain calcification. Aran et al, 2016 - 6 patients from 4 unrealted consang Pakistani families - hom nonsense mutation R839*. It segregated with disease in all families and haplotype analysis indicated a founder effect. Analysis of cells from 1 carrier indicated the mutation results in nonsense mediated mRNA decay nd likely a complete LOF. Nocilas et al, 2017 - 4 diff het missense variants in 4/79 patients with brain calcifications. ll found at low freq in ExAC - no functional studies or segregtion performed - 3 missese the 4th is the stop variant prev reported. Suzuki-Muromoto et al, Japnese patient cpmound het for truncating variants - this patients phenotype not the same as those in the Aran et al paper - patient had multifocal 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
Microcephaly, seizures, spasticity, and brain calcification, 251280

Publications

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. At least 3 truncating variants identified, one variant has been shown to be a founder in four consanguineous Palestinian Israeli families following haplotype analysis, however, functional studies demonstrate nonsense-mediated mRNA decay and likely a complete loss of function in the cells from one affected family member (PMID 27164683). The other two variants were found as compound heterozygotes in a Japanese patient with dyskinetic cerebral palsy and epilepsy (PMID 28804758).
Created: 12 Nov 2018, 1:05 p.m.

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Please note additional publications to support gene-disease association.
Created: 18 Aug 2018, 9:19 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microcephaly, seizures, spasticity, and brain calcification, MIM#251280

Publications

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

Ellen McDonagh (Genomics England Curator)

Red List (low evidence)

This gene was added and reviewed by an external reviewer as red to the Epilepsy Plus gene panel on 10th May 2017. One study reporting multiple consanguineous families with the same founder mutation, for a recessive syndrome characterized by prenatal hyperechogenic brain foci, congenital microcephaly, hypothalamic midbrain dysplasia, epilepsy, and profound global developmental disability.
Created: 18 Dec 2017, 12:21 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Cristina Dias (The Francis Crick Institute)

Red List (low evidence)

4 consanguineous families with the same mutation (c.2515C.T, p.R839X) described by Aran et al (2016) Neurology 86(21):2016-2024.
Created: 10 May 2017, 9:15 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
intellectual disability; microcephaly; epilepsy; perithalamic hyperechogenicity; periventricular hyperechogenicity; midbrain abnormalities; hypothalamic abnormalities

Publications

History Filter Activity

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to PCDH12.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to PCDH12.

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Cristina Dias: 4 consanguineous families with

12 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: pcdh12 has been classified as Green List (High Evidence).

12 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: pcdh12 has been classified as Green List (High Evidence).

12 Nov 2018, Gel status: 1

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: pcdh12 has been classified as Red List (Low Evidence).

12 Nov 2018, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: PCDH12 were changed from intellectual disability; microcephaly; epilepsy; perithalamic hyperechogenicity; periventricular hyperechogenicity; midbrain abnormalities; hypothalamic abnormalities to Microcephaly, seizures, spasticity, and brain calcification 251280

12 Nov 2018, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: PCDH12 were set to 27164683

4 Apr 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

PCDH12 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review

4 Apr 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

PCDH12 was created by Sarah Leigh