Intellectual disability - microarray and sequencing
Gene: FMR1
Although the majority of Fragile-X syndrome (FXS) cases are caused by CGG-repeat expansions in the FMR1 gene, rare deletions, point mutations and missense variants have also been associated with a FXS phenotype and are supported by functional studies (PMID: 21267007; 25171808; 28176767; 29178241). Therefore, a Green rating for the FMR1 gene entity on the ID panel (main feature of FXS) is justified.Created: 14 Nov 2022, 11:22 a.m. | Last Modified: 14 Nov 2022, 11:22 a.m.
Panel Version: 3.1759
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
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
PREMATURE OVARIAN FAILURE SYNDROME TYPE 1 (POF1)
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_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_gilissen_2014_known;in_omim_20150205_movement;in_movement_disorder_list;in_UKGTN_v12 . Main mutation mechanism : Loss of function; Activating; UncertainCreated: 27 Jul 2017, 5:53 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; find_uk10k; gilissen_2014_known; omim_20150205_movement; sfari_20150206; manju_list; UKGTN_v12; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; GEL_ID_green_20160217; neuro_20160418_strict; Loss of function; Activating; Uncertain. 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, 12:28 p.m.
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
Comment on mode of pathogenicity: Nucleotide repeat expansion in the majority of affected individuals. Tagged 5.12.16 by Alice GardhamCreated: 5 Dec 2016, 11:23 a.m.
Comment on mode of pathogenicity: Nucleotide repeat expansion. Tagged 5.12.16 by Alice GardhamCreated: 5 Dec 2016, 11:20 a.m.
Publications for gene: FMR1 were set to
Phenotypes for gene: FMR1 were changed from Fragile X syndrome, 300624Fragile X tremor/ataxia syndrome, 300623Premature ovarian failure 1, 311360; PREMATURE OVARIAN FAILURE SYNDROME TYPE 1 (POF1) to Fragile X syndrome, OMIM:300624; Fragile X tremor/ataxia syndrome, OMIM:300623
Tag currently-ngs-unreportable was removed from gene: FMR1.
Source Victorian Clinical Genetics Services was added to FMR1.
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.
Mode of pathogenicity for FMR1 was changed to Other - please provide details in the comments
Mode of pathogenicity for FMR1 was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
FMR1 was added to Intellectual disabilitypanel. Source: Expert Review Green
Model of inheritance for gene FMR1 was changed to X-LINKED: hemizygous mutation in males, may be caused by monoallelic mutations in females
FMR1 was added to Intellectual disabilitypanel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen
Model of inheritance for gene FMR1 was changed to X-LINKED: hemizygous mutation in males, may be caused by monoallelic mutations in females
FMR1 was added to Intellectual disabilitypanel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen
FMR1 was added to Intellectual disabilitypanel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen