Early onset or syndromic epilepsy
Gene: PIGA
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Comment on mode of inheritance: Kept Mode of Inheritance as XLR based on post-Webex review by Helen Lord.Created: 7 Sep 2019, 11:46 a.m. | Last Modified: 7 Sep 2019, 11:46 a.m.
Panel Version: 1.287
Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.
Panel Version: 1.262
Comment on mode of inheritance: OMIM records XLR inheritance for 'Multiple congenital anomalies-hypotonia-seizures syndrome 2 (MIM:300868). Gene2Phenotype reports 'hemizygous' allelic requirement for MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2. Johnston et al., 2012 (PMID:22305531) report 3 deceased males and 2 carrier females. Both carrier females had 100% skewed X-inactivation and neither presented with a phenotype.Created: 13 Aug 2019, 1:14 p.m. | Last Modified: 13 Aug 2019, 1:14 p.m.
Panel Version: 1.209
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
XLR multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2). Myoclonic seizures are a feature. Johnston et al, 2012 - germline nonsense mutation in 2 aff boys, 2 females - obligate carriers and had 100% skewed X-inactivation. Functional studies done. Claes et al, 1997 & Belat et al, 2014 - 1 patient - hemizygous truncating mutation. Not seen in 4 healthy males and was present in 3 unaff female relatives. Kato et al, 2014 - 5 boys from 4 unrelated families - hemizygous mutations - in vitro functional studies done. Swoboda et al, 2014 - 2 aff males from a large family had a hemizygous in frame 3bp del - expression studies support pathogenicity. Fauth et al 2016 - 4 male patients from 3 unrealted families - sme hemizygous nonsesne mutation R412*, het in two clinically unaffected mothers.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Multiple congenital anomalies-hypotonia-seizures syndrome,300868; Paroxysmal nocturnal hemoglobinuria, somatic,300818
Publications
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on mode of inheritance: G2P and OMIM both state biallelic in females, confirmed with reviewer.Created: 29 Jan 2016, 5:03 p.m.
Comment on phenotypes: Sourced from OMIM.Created: 21 Jan 2016, 11:27 a.m.
Gene added in expert review of the panel by Richard Scott (Genomics England), Manju Kurian (UCL-Institute of Child Health), Natalie Trump (NHS - Great Ormond Street Hospital), Amy McTague (UCL Institute of Child Health).Created: 12 Nov 2015, 4:18 p.m.
Tag Skewed X-inactivation tag was added to gene: PIGA.
Gene: piga has been classified as Green List (High Evidence).
Mode of inheritance for gene: PIGA was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: PIGA were changed from Multiple congenital anomalies-hypotonia-seizures syndrome 2 to Multiple congenital anomalies-hypotonia-seizures syndrome 2, 300868
Publications for gene: PIGA were set to Johnston et al (2012) Am J Hum Genet 90, 295 300
Mode of inheritance for gene: PIGA was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Source Wessex and West Midlands GLH was added to PIGA.
Source NHS GMS was added to PIGA.
Ellen McDonagh: Gene added in expert review of
NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to PIGA. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to PIGA. Panel: Genetic Epilepsy Syndromes
PIGA was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review,Expert Review Green
PIGA was created by Sarah Leigh