Early onset or syndromic epilepsy
Gene: PIGO
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
AR hyperphosphatasia with mental retardation syndrome 2. Some patients have additional features incl seizures. Krawitz et al, 2012 - 2 sisters born of unrelated British parents (compound het for 2 PIGO mutations) and an unrelated girl with MR. The unrelated girl died of seizures at 22 months (compound het for two PIGO mutations) - in vitro functional expression studies done. Tanigawa et al, 2017 - new patients with PIGO mutation and also summarising against cases reported by Krawitz et al, 2012, Kuki et al, 2013, Nakamura et al, 2014 & Xue et al, 2016 - 7/11 had seizures from 6 families.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
Hyperphosphatasia with mental retardation syndrome, 614749
Publications
Comment when marking as ready: Sufficient cases with compound heterozygous mutations in PIGO and 3 cases with seizures.Created: 21 Nov 2018, 11:38 a.m.
Comment on publications: Further cases reported in PMIDs: 28900819 and 28337824Created: 21 Nov 2018, 11:20 a.m.
Comment on list classification: Sufficient cases with compound heterozygous mutations in PIGO and 3 cases with seizures.Created: 21 Nov 2018, 11:03 a.m.
PIGO is associated with Hyperphosphatasia with mental retardation syndrome 2 in OMIM and Gene2Phenotype (confirmed).
3 individuals from 2 families reported by Krawitz et al 2012 (PMID: 22683086). In family A two sisters are compound heterozygous for c.2869C>T and c.2361dup. In family B the affected individual is compound heterozygous c.2869C>T and c.3069+5G>A. The affected individual in family B presented with seizures.
Kuki et al 2013 (PMID: 24049131) reports case of 9 year old boy with deafness, tetralogy of Fallot, and Hirschsprung disease; showed muscular hypotonia and facial dysmorphism; and had short fingers with hypoplasia of the distal phalanges. At 1 year of age, he began to have intractable partial seizures. Two mutations were detected in PIGO, c.355C.T (p.Arg119Trp; NM_032634) and c.2497_2498del ,leading to a frameshift mutation, p.Ala834fs.
Nakamura et al 2014 (PMID: 24417746) reports 2 siblings with severe epileptic seizures, developmental delay, and mild elevation of ALP and compound heterozygous mutations in PIGO c.389C>A (p.Thr130Asn) and c.1288C>T (p.Gln430*).
Summary: >3 cases/families of compound heterozygous mutations in PIGO in patients with Hyperphosphatasia with mental retardation syndrome 2 and 3 cases with seizures.Created: 21 Nov 2018, 11:01 a.m.
Seizures are part of the phenotype of this metabolic disorder.Created: 18 Aug 2018, 10:43 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hyperphosphatasia with mental retardation syndrome 2, MIM#614749
Publications
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to PIGO.
Source NHS GMS was added to PIGO.
Zornitza Stark: Seizures are part of the pheno
Gene: pigo has been classified as Green List (High Evidence).
Publications for gene: PIGO were set to 22683086; 24049131; 24417746; 28900819
Phenotypes for gene: PIGO were changed from to Hyperphosphatasia with mental retardation syndrome 2, 614749
Publications for gene: PIGO were set to
Mode of inheritance for gene: PIGO was changed from to BIALLELIC, autosomal or pseudoautosomal
Gene: pigo has been classified as Green List (High Evidence).
Expert Review Amber was added to PIGO. Panel: Genetic Epilepsy Syndromes
PIGO was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
PIGO was created by Sarah Leigh