Intellectual disability - microarray and sequencing
Gene: FLVCR1The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.
Panel Version: 3.1510
Comment on list classification: Leaving this gene green for now, but only one case where intellectual disability was reported. This gene should be updated at the next GMS review.Created: 8 Oct 2020, 3:30 p.m. | Last Modified: 8 Oct 2020, 3:30 p.m.
Panel Version: 3.400
Associated with Ataxia, posterior column, with retinitis pigmentosa #609033 in OMIM. The clinical synopsis in OMIM notes that mental retardation was only see in one family.
Summary: many (~10) cases reported with varying degrees of Ataxia, posterior column, with retinitis pigmentosa but intellectual disability only reported in one case.
PMID: 30656474 - Kuehlewein et al 2019 - Six individuals with retinitis pigmentosa (RP) carrying mutations in the FLVCR1 gene underwent detailed ophthalmological examinations and two of these also an extensive neurological examination. Variants included one nonsense mutation, one 1-bp deletion, two missense variants, and one splice site variant. Mutations in FLVCR1 can present with the clinical picture of a non-syndromic autosomal recessive RP (in this case RP without PCA), RP with mild cerebellar signs, but also PCARP. No intellectual disability was reported.
PMID: 22279524 - Puffenberger et al 2012 - report a case from a Plain population from Pennsylvania (Swiss decent) where 1 individual with Posterior column ataxia with retinitis pigmentosa had a homozygous variant in FLVCR1 (c.361A>G, p.Asn121Asp), which is the same as reported in the large German-Swiss decent family by Rajadhyaksha et al 2010. No intellectual disability reported but detailed phenotype information not given.
PMID:21267618 - Ishiura et al 2011 - Japanese consanguineous family with Posterior column ataxia with retinitis pigmentosa (PCARP). Two affected siblings suffered from childhood-onset retinitis pigmentosa and slowly progressive sensory ataxia. They also showed mild mental retardation. A novel homozygous c.1477G>C (G493R) mutation in FLVCR1, cosegregated with the disease.
PMID:21070897 - Rajadhyaksha et al 2010 - from targeted sequencing of a genes in a candidate locus they report 3 families (one the family reported in Higgins et al, one French-Canadian, and one Spanish) with 3 different homozygous missense variants in FLVCR1. All affected individuals had visual problems and ataxia but no intellectual disability was reported.
PMID:9409377 - Higgins et al 1997 - report a large American pedigree of German-Swiss decent with autosomal recessive posterior column ataxia with retinitis pigmentosa. No variant data. Abstract only accessed.
Also:
PMID: 30444160 - Lee et al 2018 - Seven patients from three families were identified to have PCARP and FLVCR1 mutation. Ophthalmic features were reviewed. Abstract only accessed.Created: 8 Oct 2020, 2:21 p.m. | Last Modified: 8 Oct 2020, 2:21 p.m.
Panel Version: 3.394
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Progressive neurological condition, ID is not really part of the phenotype.Created: 3 Feb 2020, 3:44 a.m. | Last Modified: 3 Feb 2020, 3:44 a.m.
Panel Version: 3.0
Phenotypes
Ataxia, posterior column, with retinitis pigmentosa, MIM#609033
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_omim_20150205_movement . Main mutation mechanism : All missense/in frameCreated: 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; gilissen_2014_candidate; omim_20150205_movement; Nijmegen_ID_diagnostic; GEL_ID_green_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, 12:28 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Mode of pathogenicity
Other
Comment on list classification: Confirmed DD geneCreated: 7 Feb 2016, 8:31 p.m.
Tag for-review was removed from gene: FLVCR1.
Source Expert Review Red was added to FLVCR1. Rating Changed from Green List (high evidence) to Red List (low evidence)
Tag for-review tag was added to gene: FLVCR1.
Gene: flvcr1 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.
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
FLVCR1 was created by ellenmcdonagh
FLVCR1 was added to Intellectual disabilitypanel. Sources: Expert Review Amber