Early onset or syndromic epilepsy
Gene: NRXN1
2 cases of hom/compound het variants assoc with a sever recessive MR syndrome - patients had severe epilepsyCreated: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.
Panel Version: 1.261
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Comment on mode of inheritance: Kept Mode of Inheritance as 'BOTH monoallelic and biallelic' based on post-Webex review by Helen Lord.Created: 7 Sep 2019, 11:42 a.m. | Last Modified: 7 Sep 2019, 11:42 a.m.
Panel Version: 1.284
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: PMID:30031152 (Al Shehhi et al.) report heterozygous deletions of NRXN1 with phenotypes including seizures. At least PMID:21964664 (Harrison et al.) and PMID:19896112 report a biallelic mode of inheritance.Created: 13 Aug 2019, 12:53 p.m. | Last Modified: 13 Aug 2019, 12:53 p.m.
Panel Version: 1.203
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
Moller et al 2013 - idiopathic generalised epilepsy. AR Pitt Hopkins like syndrome 2 - epilepsy a feature in 2/3 patients. Zweier et al, 2009 - compound het in an affected girl (stop mutation and a gross del). Harrison et al, 2011 - 2 sisters - severe early onset MR and severe epilepsy - compound het deletions. On HGMD Pro variants reported in this gene assocaited with autism spectrum disorder - not many mention of epilepsy. In addition most variants are gross deletions including some of the gene.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
Pitt-Hopkins-like syndrome 2 614325; {Schizophrenia, susceptibility to, 17}, 614332
Publications
Comment when marking as ready: Associated with phenotypes in OMIM and as probable Gen2Phen gene for both Pitt-Hopkins-like syndrome 2 and autism. Numerous variants reported in mono or biallelic form in cases displaying a wide range of neurodevelopmental disorders with varied features, including seizures.Created: 3 Sep 2018, 2:52 p.m.
Comment on phenotypes: Some cases of {Schizophrenia, susceptibility to, 17} 614332 and autism also display seizures.Created: 3 Sep 2018, 2:49 p.m.
Seizures are part of the phenotype of both NRXN1 deletions and of bi-allelic variants.Created: 17 Aug 2018, 11:17 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Pitt-Hopkins-like syndrome 2, MIM#614325
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Pitt-Hopkins-like syndrome 2 (AR); severe intellectual disability (AD)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Pitt-Hopkins-like syndrome 2 (AR); severe intellectual disability (AD)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Pitt-Hopkins-like syndrome 2 (AR); severe intellectual disability (AD)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Pitt-Hopkins-like syndrome 2 (AR); severe intellectual disability (AD)
Publications
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: NRXN1 were changed from Pitt-Hopkins-like syndrome 2, 614325 to Pitt-Hopkins-like syndrome 2, OMIM:614325 (AR); Complex neurodevelopmental disorder (AD)
Gene: nrxn1 has been classified as Green List (High Evidence).
Publications for gene: NRXN1 were set to 21964664; 19896112; 30031152; 23533028
Mode of inheritance for gene: NRXN1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of inheritance for gene: NRXN1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Source Wessex and West Midlands GLH was added to NRXN1.
Source NHS GMS was added to NRXN1.
Zornitza Stark: Seizures are part of the pheno
Gene: nrxn1 has been classified as Green List (High Evidence).
Gene: nrxn1 has been classified as Green List (High Evidence).
Mode of inheritance for gene: NRXN1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: NRXN1 were set to Pitt-Hopkins-like syndrome 2, 614325
Phenotypes for gene: NRXN1 were set to Pitt-Hopkins-like syndrome 2, 614325
Publications for gene: NRXN1 were set to 21964664; 19896112; 30031152; 23533028
Expert Review Amber was added to NRXN1. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to NRXN1. Panel: Genetic Epilepsy Syndromes
NRXN1 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Red,Expert,UKGTN
NRXN1 was created by Sarah Leigh