Intellectual disability - microarray and sequencing
Gene: IGF1R
Patients with compound heterozygous/homozygous variants in this gene are reported as having ID, ranging from mild to moderate (26252249). No evidence heterozygous variants cause ID.Created: 19 Jun 2018, 6:42 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment when marking as ready: Resistance to insulin-like growth factor 1 presents with growth restriction (pre-natal onwards). Although some have been noted to have developmental delay this is reportedly mild. Therefore on the current evidence this phenotype is not a clear fit for this panel.Created: 21 Dec 2017, 11 a.m.
Comment on list classification: Resistance to insulin-like growth factor 1 presents with growth restriction (pre-natal onwards). Although some have been noted to have developmental delay this is reportedly mild. Therefore on the current evidence this phenotype is not a clear fit for this panel.Created: 21 Dec 2017, 10:59 a.m.
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_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf . Main mutation mechanism : Loss of functionCreated: 27 Jul 2017, 6:48 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; neuro_20160418_strict; Loss of function. 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, 12:40 p.m.
Mode of inheritance
Unknown
Publications
Comment on list classification: Changed from Amber to Green. After clinical review-ID /delayed cases seem to have biallelic variants (on the whole), so a green rating for biallelic variants would be acceptable. Less convincing evidence for monoallelic setting.Created: 29 Aug 2018, 3:04 p.m.
Referred to clinical team for review, in view of green review from external clinician, addition of a publication supporting developmental delay in 4 cases (although noted the cases are defined as having Developmental delay/ID), and that gene is currently listed as a diagnostic gene on VCGS intellectual disability panelCreated: 8 Aug 2018, 3:38 p.m.
Comment on publications: added further publications to support gene-disease association and publications suggested from external reviewerCreated: 8 Aug 2018, 3:17 p.m.
from Prontera et al., (2015) PMID: 26252249 : Heterozygous mutations in the IGF1R gene, causing partial resistance to IGFI, have been detected in patients with nonsyndromic IUGR and postnatal growth failure (Kawashima et al., 2005; Wall-born et al., 2010), whereas to date, four patients have now been described harboring biallelic mutations in IGF1R (Abuzzahab et al., 2003; Fang et al., 2012; Gannage-Yared et al., 2013; Prontera et al., (2015). The latter displays a more severe phenotype mainly characterized by IUGR, short stature, developmental and speech delay, microcephaly, facial dysmorphism, heart malformation, and reduced subcutaneous fat. In Prontera et al., (2015) PMID: 26252249 the reported patient shared many clinical (IUGR, short stature, lipodystrophy, microcephaly, developmen-tal delay), dysmorphic, malformative (narrowed pulmonary brancharteries), and metabolic (high triglyceride, calcium, and phosphorus) features with the reported cases.
Created: 8 Aug 2018, 3:14 p.m.
Comment on list classification: This gene is from an expert list and needs further assessment by the Genomics England curation team to assess inclusion and pertinence to this panel.Created: 20 Jul 2017, 12:05 p.m.
Phenotypes for gene: IGF1R were changed from Gene2Phenotype confirmed gene with ID HPO; Insulin-like growth factor I, resistance to, 270450; developmental delay to Insulin-like growth factor I, resistance to, OMIM:270450
Source Victorian Clinical Genetics Services was added to IGF1R.
Gene: igf1r has been classified as Green List (High Evidence).
Phenotypes for gene: IGF1R were set to Gene2Phenotype confirmed gene with ID HPO; Insulin-like growth factor I, resistance to, 270450; developmental delay
Publications for gene: IGF1R were set to 25529582; 26252249; 22130793; 14657428; 23045302
Phenotypes for gene: IGF1R were set to Gene2Phenotype confirmed gene with ID HPO; Insulin-like growth factor I, resistance to, 270450; intellectual disability
Publications for gene: IGF1R were set to 25529582; 26252249
Publications for gene: IGF1R were set to 25529582; 26252249
Publications for gene: IGF1R were set to 25529582; 26252249
Phenotypes for gene: IGF1R were set to Gene2Phenotype confirmed gene with ID HPO; Insulin-like growth factor I, resistance to, 270450
Mode of inheritance for gene: IGF1R was changed from Other - please specify in evaluation comments to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: IGF1R was changed from Other - please specify in evaluation comments to BIALLELIC, autosomal or pseudoautosomal
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.
This gene has been classified as Amber List (Moderate Evidence).
IGF1R was created by BRIDGE
IGF1R was added to Intellectual disabilitypanel. Sources: BRIDGE study SPEED NEURO Tier1 Gene