Intellectual disability - microarray and sequencing
Gene: ERLIN2
Comment on mode of inheritance: : Biallelic variants in ERLIN2 are known to cause recessive HSP type SPG18 (PMID:21330303, 21796390, 23085305) these cases are described with ID phenotype. Recently (2018) two families with an autosomal dominant, pure form of HSP caused by a novel ERLIN2 heterozygous missense variant were described PMID:29528531, these cases did not have intellectual disability and are not represented by this entry.Created: 10 Aug 2018, 3:21 p.m.
Comment on list classification: changed from Amber to Green. More than unrelated cases with intellectual disability and HSPCreated: 10 Aug 2018, 10:53 a.m.
Initial candidate gene case described in PMID: 21937992 there are more than unrelated families who have been reported on inactivating ERLIN2 mutations in patients with recessive intellectual disability and progressive motor dysfunction PMID: 21330303, PMID: 21796390; 23085305 (biallelic) and more recently individuals described with dominant pure hereditary spastic paraplegia PMID: 29528531;28832565 (monoallelic), however the index cases did not have intellectual disability.
Created: 10 Aug 2018, 10:45 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
AUTOSOMAL RECESSIVE MENTAL RETARDATION
Publications
This is a possible DD gene in Gene2Phenotype for AUTOSOMAL RECESSIVE MENTAL RETARDATION. Two publications describing progressive decline in ID in the probands (under the age of 20).Created: 27 Oct 2017, 2:46 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spastic paraplegia 18, autosomal recessive 611225
Publications
This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_2_4_2017;in_omim_20150205_movement;in_movement_disorder_list . Main mutation mechanism : All missense/in frameCreated: 27 Jul 2017, 5:39 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; find_uk10k; gilissen_2014_candidate; omim_20150205_movement; manju_list; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; GEL_ID_red_20160217; neuro_20160418_strict; All missense/in frame. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation TrustCreated: 19 Jul 2017, 12:23 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Mode of pathogenicity
Other
Phenotypes for gene: ERLIN2 were set to Spastic paraplegia 18, autosomal recessive, 611225; intellectual disability; AUTOSOMAL RECESSIVE MENTAL RETARDATION
Phenotypes for gene: ERLIN2 were set to Spastic paraplegia 18, autosomal recessive, 611225; intellectual disability
Mode of inheritance for gene: ERLIN2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ERLIN2 were set to Spastic paraplegia 18, autosomal recessive, 611225; Spastic paraplegia autosomal dominant; Intellectual disability; hereditary spastic paraplegia; neurodegeneration
Mode of inheritance for gene: ERLIN2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: ERLIN2 were set to Spastic paraplegia 18, autosomal recessive, 611225; Spastic paraplegia autosomal dominant; Intellectual disability; hereditary spastic paraplegia; neurodegeneration
Gene: erlin2 has been classified as Green List (High Evidence).
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
Expert Review Amber was added to ERLIN2. Panel: Intellectual disability Publications for gene ERLIN2 was set to ['27824013', '25977983', '23897027', '23109145', '23109142', '23085305', '22554690', '21796390', '21330303']
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
ERLIN2 was added to Intellectual disabilitypanel. Source: Expert Review Red Model of inheritance for gene ERLIN2 was set to BIALLELIC, autosomal or pseudoautosomal
ERLIN2 was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen