Intellectual disability - microarray and sequencing
Gene: FLNA
The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 9:34 a.m. | Last Modified: 11 Oct 2023, 9:34 a.m.
Panel Version: 5.286
In accordance with the review by Tracy Lester (Genetics laboratory, Oxford UK), the relevance of this gene on this panel should be reassessed. It would appear that intellectual disability is a rare phenotypic feature in FLNA variant carriers and if present the manifestation is mild.Created: 6 Jun 2023, 1:43 p.m. | Last Modified: 6 Jun 2023, 1:43 p.m.
Panel Version: 5.180
There is no evidence that this gene causes intellectual disability in the absence of other features. GeneReviews notes:
Intelligence is normal to borderline. Formal cognitive testing of ten affected individuals (2 males, 8 females) with FLNA loss-of-function variants demonstrated an average IQ of 95, but also a strikingly high number of affected individuals with dyslexia [Chang et al 2005, Chang et al 2007, Reinstein et al 2012]. However, these results likely reflect a selection bias towards more severely affected individuals, since those with normal cognitive function usually would not have undergone a screening brain MRI or molecular testing.
I think the gene should be downgraded to amber for this panel until more evidence is provided. The gene is assocaited with periventricular nodular heterotopia (PVNH) so the gene should remain on the epilepsy and brain abnormalities panels.Created: 24 May 2023, 11:53 a.m. | Last Modified: 24 May 2023, 11:53 a.m.
Panel Version: 5.152
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Skeletal dysplasia
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
EPILEPTIC ENCEPHALOPATHY
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_UKGTN_v12 . Main mutation mechanism : Loss of function; Uncertain; All missense/in frameCreated: 27 Jul 2017, 5:52 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; UKGTN_v12; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; GEL_ID_green_20160217; neuro_20160418_strict; Loss of function; Uncertain; 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, 12:27 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
Mode of pathogenicity
Tag Q2_23_demote_red was removed from gene: FLNA.
Source Expert Review Red was added to FLNA. Source NHS GMS was added to FLNA. Rating Changed from Green List (high evidence) to Red List (low evidence)
Tag Q2_23_demote_red tag was added to gene: FLNA.
Publications for gene: FLNA were set to
Phenotypes for gene: FLNA were changed from Frontometaphyseal dysplasia, 305620Heterotopia, periventricular, ED variant, 300537FG syndrome 2, 300321Cardiac valvular dysplasia, X-linked, 314400Terminal osseous dysplasia, 300244Congenital short bowel syndrome, 300048; EPILEPTIC ENCEPHALOPATHY to Heterotopia, periventricular, 1, OMIM:300049; Otopalatodigital syndrome, type II, OMIM:304120; ?FG syndrome 2, OMIM:300321
Source Victorian Clinical Genetics Services was added to FLNA.
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.
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
FLNA was added to Intellectual disabilitypanel. Source: Expert Review Green
Model of inheritance for gene FLNA was changed to X-LINKED: hemizygous mutation in males, may be caused by monoallelic mutations in females
FLNA was added to Intellectual disabilitypanel. Sources: Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen
FLNA was added to Intellectual disabilitypanel. Sources: Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen