FLNA

Syndromic associated CHDs overview

Mitral atresia (1, 16.7%)

Aortic valvar stenosis - congenital (1, 16.7%)

Aortic coarctation (2, 33.3%)

Aortic regurgitation - congenital (2, 33.3%)

[edit] Synopsis

Filamins stabilize F-actin networks in the cell and link them to cellular membranes by binding to transmembrane receptors or ion channels, thereby regulating cell morphology, membrane integrity and cell locomotion. FLNA is highly expressed in early myotubes, developing myofibrils and migratory neurons. Dysfunction of the X-linked FLNA gene leads to abnormalities in outflow tract development, often manifesting as a mitral or aortic valve insufficiency and a cerebral migration disorder (Sheen VL et al., 2001).

[edit] Mutation screens

Congenital malformations of the cerebral cortex (cerebral periventricular nodular heterotopia (PNH) (OMIM:300017)) are ascribed to mutations in the gene FLNA. de Wit MC et al., 2011 reported on congenital heart defects in 5 out of 6 PNH patients with mutations in FLNA. The spectrum of heart defects associated with FLNA mutations mainly involves obstruction of the left ventricle outflow tract.

External references for FLNA

• ensembl: ENSG00000196924
• OMIM: 300017
• Search miRBase for FLNA
• Expression patterns from 4DXPress: FLNA
• MGI: MGI:95556
• ZFIN: ZDB-GENE-030131-2145
• Wikipedia: FLNA
• Search Wikiproteins: FLNA
• Search Genetic Association Database: FLNA
• Search GeneTests: FLNA
• CHeartED:

Known phenotypes for FLNA

Non-syndromic

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Syndromic

Aortic coarctation

Support: likely: 2 or more patients (with CHD and a mutation in the candidate gene) References: PMID:20730588 (population study with screening of similar CHD patients and normal controls ) Syndromes: X-linked dominant periventricular heterotopia (OMIM:300049): hemizygous males tend to die in utero. Affected females usually present with epilepsy, but have normal intelligence. Additional features include defects of the cardiovascular system, such as patent ductus arteriosus, bicuspid aortic valve, and dilation of the sinuses of Valsalva or the thoracic aorta. Incidence: Comments: Studies: (1) [ show ] [ hide ] Reference: PMID:20730588 Incidence: 2/6 patients Comments: de Wit MC et al., 2011 reported on congenital heart defects in 5 out of 6 PNH patients with mutations in FLNA. The spectrum of heart defects associated with FLNA mutations mainly involves obstruction of the left ventricle outflow tract: aortic valve insufficiency, aortic valve stenosis, aortic coarctation or mitral valve atresia with hypoplastic LV. Add another study.

Aortic regurgitation - congenital

Support: likely: 2 or more patients (with CHD and a mutation in the candidate gene) References: PMID:20730588 (population study with screening of similar CHD patients and normal controls ) Syndromes: X-linked dominant periventricular heterotopia (OMIM:300049): hemizygous males tend to die in utero. Affected females usually present with epilepsy, but have normal intelligence. Additional features include defects of the cardiovascular system, such as patent ductus arteriosus, bicuspid aortic valve, and dilation of the sinuses of Valsalva or the thoracic aorta. Incidence: Comments: Studies: (1) [ show ] [ hide ] Reference: PMID:20730588 Incidence: 2/6 patients Comments: de Wit MC et al., 2011 reported on congenital heart defects in 5 out of 6 PNH patients with mutations in FLNA. The spectrum of heart defects associated with FLNA mutations mainly involves obstruction of the left ventricle outflow tract: aortic valve insufficiency, aortic valve stenosis, aortic coarctation or mitral valve atresia with hypoplastic LV. Add another study.

Aortic valvar stenosis - congenital

Support: unconfirmed: a single case report References: PMID:20730588 (population study with screening of similar CHD patients and normal controls ) Syndromes: X-linked dominant periventricular heterotopia (OMIM:300049): hemizygous males tend to die in utero. Affected females usually present with epilepsy, but have normal intelligence. Additional features include defects of the cardiovascular system, such as patent ductus arteriosus, bicuspid aortic valve, and dilation of the sinuses of Valsalva or the thoracic aorta. Incidence: Comments: Studies: (1) [ show ] [ hide ] Reference: PMID:20730588 Incidence: 1/6 patients Comments: de Wit MC et al., 2011 reported on congenital heart defects in 5 out of 6 PNH patients with mutations in FLNA. The spectrum of heart defects associated with FLNA mutations mainly involves obstruction of the left ventricle outflow tract: aortic valve insufficiency, aortic valve stenosis, aortic coarctation or mitral valve atresia with hypoplastic LV. Add another study.

Mitral atresia

Support: unconfirmed: a single case report References: PMID:20730588 (population study with screening of similar CHD patients and normal controls ) Syndromes: X-linked dominant periventricular heterotopia (OMIM:300049): hemizygous males tend to die in utero. Affected females usually present with epilepsy, but have normal intelligence. Additional features include defects of the cardiovascular system, such as patent ductus arteriosus, bicuspid aortic valve, and dilation of the sinuses of Valsalva or the thoracic aorta. Incidence: Comments: Studies: (1) [ show ] [ hide ] Reference: PMID:20730588 Incidence: 1/6 patients Comments: de Wit MC et al., 2011 reported on congenital heart defects in 5 out of 6 PNH patients with mutations in FLNA. The spectrum of heart defects associated with FLNA mutations mainly involves obstruction of the left ventricle outflow tract: aortic valve insufficiency, aortic valve stenosis, aortic coarctation or mitral valve atresia with hypoplastic LV. Add another study.

Patent arterial duct (PDA)

Support: confirmed: 2 or more independent reports > 1% incidence References: PMID:9883725 (basic research ) Syndromes: X-linked dominant periventricular heterotopia (OMIM:300049): hemizygous males tend to die in utero. Affected females usually present with epilepsy, but have normal intelligence. Additional features include defects of the cardiovascular system, such as patent ductus arteriosus, bicuspid aortic valve, and dilation of the sinuses of Valsalva or the thoracic aorta. Incidence: Comments: Studies: (0) [ show ] [ hide ] Add another study.

Add another phenotype.

Protein interaction partners

Patients reports for FLNA

• case 2 Clinical data Phenotype

Translocations

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Mutations in FLNA

Mutation (DNA)	Mutation (peptide)	CHD	Reference	Other features	Inheritence	Additional info.
c.3582delC		Aortic valvar stenosis - congenital	PMID:20730588	Female patient with normal IQ, PNH and generalized seizures.	X-linked Sporadic	show hide Genetic evidence not tested in parents or normal controls. in silico prediction Functional studies No functional studies were performed for this variant. Comments
c.3045del5		Aortic regurgitation - congenital	PMID:20730588	Normally developing female patient with PNH, but without seizures.	X-linked Sporadic	show hide Genetic evidence not tested in parents or in normal controls. in silico prediction Functional studies No functional studies were performed. Comments
c.6635delTCAG		Aortic regurgitation - congenital	PMID:20730588	Female patient with VSD and aortic regurgitation; bilateral PNH and an enlarged retrocerebellar space.	X-linked Sporadic	show hide Genetic evidence not tested in parents or in normal controls. in silico prediction Functional studies No functional studies were performed for this variant. Comments
c.5290G>A	p.1764A>T	Mitral atresia	PMID:20730588	Male patient with complex CHD, preauricular pit, bilateral PNH. Patient died neonatally due to heart failure.	X-linked Sporadic	show hide Genetic evidence not tested in parents or normal controls. in silico prediction Functional studies The missense change c.5290G>A has been reported before in a woman with PNH and has been described as pathogenic, although there is no definitive evidence: no functional studies were performed. Comments
c.220G>A	p.74G>R	Aortic coarctation	PMID:20730588	Female patient with ASD, aortic coarctation and regurgitation. She showed normal to mildly delayed cognitive development and delayed motor development with hypotonia and severe hyperlaxity. Facial features included a broad forehead, prominent orbital ridges, deep set eyes with down-slant, and a flat midface. No seizures. Brain MRI showed bilateral PNH and an enlarged retrocerebellar cyst. Congenital lobar emphysema.	X-linked Familial	show hide Genetic evidence Segregating inherited from mother with PNH and epilepsy. Not present in maternal grandparents. in silico prediction Functional studies No functional studies were performed. Comments

Representation of protein FLNA

Heart expression domain of FLNA

No specified expression domain for FLNA

Add a new domain where gene FLNA is expressed

Associated CHDs found by automated text mining

AGeneApart Method

Huge Navigator (Genopedia)

See complete results on Genopedia (including non CHD)

Heart defects

This page contributors

• Jeroen Breckpot - CME Leuven (Belgium) (association, mutation, study, Free text)