Skeletal dysplasia
Gene: FLNA
Filamin group and related disorder gp of SD - many cases reported with missense variants or in-frame dels, often recurrent (eg c.5217G>A in TOD, exon 22 variants in MNS). Other disorders associated with this gene include - cardiac valvular dysplasia - 314400, PVNH - 300049 and neuronal intestinal pseudoobstruction (3000048). LOF/fs associated with non-skeletal phenotypes, eg PVNH; Review on behalf of Tracy LesterCreated: 6 Mar 2019, 11:44 a.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)
Phenotypes
Melnick Needles syndrome 309350; Otopalatodigital syndrome, type I -311300; Otopalatodigital syndrome, type II -304120; Frontometaphyseal dysplasia 305620; Terminal osseous dysplasia 300244
Mode of pathogenicity
Other - please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: FLNA; Initial rating suggestion: GreenCreated: 6 Mar 2019, 11:36 a.m.
Comment on mode of inheritance: Changed from 'other' as this option will also tier biallelic variants in females.Created: 3 Apr 2017, 3:58 p.m.
Comment on mode of inheritance: XLD or XLR and phenotype 300244 is unknownCreated: 7 Jul 2016, 11:04 a.m.
Comment on list classification: Used diagnostically by Ana Beleza (Guy's and St Thomas' NHS Foundation Trust)Created: 21 Jun 2016, 12:48 p.m.
Tier 1Created: 17 Jun 2016, 8:04 a.m.
Mode of inheritance
Other - please specify in evaluation comments
Phenotypes
Cardiac valvular dysplasia, X-linked 314400 XLR; Congenital short bowel syndrome 300048 XLR; FG syndrome 2 300321; Frontometaphyseal dysplasia 305620 XLR; Heterotopia, periventricular 300049 XLD; Heterotopia, periventricular, ED variant 300537; Intestinal pseudoobstruction, neuronal 300048 XLR; Melnick-Needles syndrome 309350 XLD; Otopalatodigital syndrome, type I 311300 XLD; Otopalatodigital syndrome, type II 304120 XLD; Terminal osseous dysplasia 300244
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: FLNA were changed from Terminal osseous dysplasia 300244; Otopalatodigital syndrome, type II -304120; Otopalatodigital syndrome, type II 304120 XLD; Otopalatodigital syndrome, type I -311300; Melnick Needles syndrome 309350; Frontometaphyseal dysplasia 305620; Frontometaphyseal dysplasia 305620 XLR; Osteodysplasty Melnick Needles 309350 XLD to Frontometaphyseal dysplasia 1, OMIM:305620; Melnick-Needles syndrome, OMIM:309350; Otopalatodigital syndrome, type I, OMIM:311300; Otopalatodigital syndrome, type II, OMIM:304120; Terminal osseous dysplasia, OMIM:300244
Added phenotypes Terminal osseous dysplasia 300244; Melnick Needles syndrome 309350; Frontometaphyseal dysplasia 305620; Otopalatodigital syndrome, type II -304120; Otopalatodigital syndrome, type I -311300 for gene: FLNA
Source NHS GMS was added to FLNA. Rating Changed from Green List (high evidence) to Green List (high evidence)
Mode of inheritance for FLNA was changed to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Promoted to version 1 9th August 2016
Mode of inheritance for FLNA was changed to Other - please specifiy in evaluation comments
Mode of inheritance for FLNA was changed to Other - please specifiy in evaluation comments
Phenotypes for FLNA were set to Osteodysplasty Melnick Needles 309350 XLD; Otopalatodigital syndrome, type II 304120 XLD; Frontometaphyseal dysplasia 305620 XLR; Terminal osseous dysplasia 300244
This gene has been classified as Green List (High Evidence).
FLNA was created by sleigh
FLNA was added to Unexplained skeletal dysplasiapanel. Sources: