Fetal anomalies
Gene: FLNA

FLNA (filamin A)
EnsemblGeneIds (GRCh38): ENSG00000196924
EnsemblGeneIds (GRCh37): ENSG00000196924
OMIM: 300017, Gene2Phenotype
FLNA is in 26 panels

1 review

Rebecca Foulger (Genomics England curator)

I don't know

Additional support for inclusion of gene on panel comes from Yates et al., 2017 (PMID:28425981, Whole-exome sequencing on deceased fetuses with ultrasound anomalies: expanding our knowledge of genetic disease during fetal development). Yates et al., identified a hemizgyous likely-pathogenic variant in FLNA in a case where the main ultrasound finding was CNS malformations (Table 1). A heterozygous variant in PTPN11 was also reported, which the authors classify as a Possible result.
Created: 24 May 2019, 10:53 a.m.

Additional evidence from PMID:30712878: De novo variant identified in FLNA from fetal exome sequencing in Petrovski et al., 2019 (Whole-exome sequencing in the evaluation of fetal stuctural anomalies: a prospective cohort study, PMID:30712878).
Created: 18 Apr 2019, 3:57 p.m.

Additional evidence from PAGE study: Potentially clinically useful variant identified in this gene from fetalexome sequencing inLord et al., 2019 (PMID:30712880).
Created: 18 Apr 2019, 3:51 p.m.

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.
Created: 24 Mar 2019, 4:30 p.m.

DDG2P rating in original PAGE list: Confirmed for OTOPALATODIGITAL SYNDROME TYPE 1, Confirmed for EPILEPTIC ENCEPHALOPATHY, Confirmed for TERMINAL OSSEOUS DYSPLASIA, Confirmed for MELNICK-NEEDLES SYNDROME, Confirmed for X-LINKED CONGENITAL IDIOPATHIC INTESTINAL PSEUDOOBSTRUCTION, Confirmed for OTOPALATODIGITAL SYNDROME TYPE 2, Confirmed for FRONTOMETAPHYSEAL DYSPLASIA, Confirmed for FG SYNDROME TYPE 2 and Confirmed for PERIVENTRICULAR NODULAR HETEROTOPIA TYPE 1.
Created: 11 Dec 2018, 9:04 a.m.

In the original PAGE file, MOI listed as Hemizgyous for OTOPALATODIGITAL SYNDROME TYPE 1,TERMINAL OSSEOUS DYSPLASIA, X-LINKED CONGENITAL IDIOPATHIC INTESTINAL PSEUDOOBSTRUCTION, OTOPALATODIGITAL SYNDROME TYPE 2, FRONTOMETAPHYSEAL DYSPLASIA and FG SYNDROME TYPE 2. In the original PAGE file, MOI listed as X-linked dominant for EPILEPTIC ENCEPHALOPATHY, MELNICK-NEEDLES SYNDROME, and PERIVENTRICULAR NODULAR HETEROTOPIA TYPE 1. In the original PAGE file, MOP listed as LOF for TERMINAL OSSEOUS DYSPLASIA, X-LINKED CONGENITAL IDIOPATHIC INTESTINAL PSEUDOOBSTRUCTION, and PERIVENTRICULAR NODULAR HETEROTOPIA TYPE 1. MOP listed as All missense/in frame for EPILEPTIC ENCEPHALOPATHY. MOP listed as Uncertain for OTOPALATODIGITAL SYNDROME TYPE 1, MELNICK-NEEDLES SYNDROME, OTOPALATODIGITAL SYNDROME TYPE 2, FRONTOMETAPHYSEAL DYSPLASIA and FG SYNDROME TYPE 2.
Created: 8 Nov 2018, 4:45 p.m.

Phenotypes
CNS malformations

Publications

30712878

Created: 8 Nov 2018, 4:45 p.m.

Panel version: 0.273

Details

Mode of Inheritance

X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Sources

PAGE DD-Gene2Phenotype
Expert Review Green

Phenotypes

TERMINAL OSSEOUS DYSPLASIA
OTOPALATODIGITAL SYNDROME TYPE 1
EPILEPTIC ENCEPHALOPATHY
MELNICK-NEEDLES SYNDROME
PERIVENTRICULAR NODULAR HETEROTOPIA TYPE 1
FG SYNDROME TYPE 2
X-LINKED CONGENITAL IDIOPATHIC INTESTINAL PSEUDOOBSTRUCTION
OTOPALATODIGITAL SYNDROME TYPE 2
FRONTOMETAPHYSEAL DYSPLASIA

OMIM

300017

Clinvar variants

Variants in FLNA

Penetrance

None

Publications

Panels with this gene