MYH7

Non syndromic associated CHDs overview

ASD (4, 25%)

Ebstein's malformation of tricuspid valve (12, 75%)

[edit] Synopsis

The structural MYH7 gene encodes the beta myosin heavy chain. Cardiac muscle myosin, along with actin, is one of the major components the contractile system of cardiac muscle (sarcomere). Myosin is a hexamer consisting of two heavy chain subunits (alpha and beta), two light chain subunits and two regulatory subunits. The subfragment-1 (S1) of MYH7 contains an ATPase site and an actin binding region, which are crucial for the movement of actin relative to myosin. The beta myosin heavy chain is expressed predominantly in fetal life and is switched on in older animals under conditions of thyroid hormone depletion/replacement and in response to some physical stresses (Krenz M et al., 2004, Hang CT et al., 2010). This shift in the MHC composition of the cardiac muscle can influence cardiac function (Miyata S et al., 2000). A cardiac-specific microRNA (miR-208) encoded by an intron of the MYH6 gene, is required for cardiomyocyte hypertrophy, fibrosis, and expression of βMHC in response to stress and hypothyroidism (Van Rooij E et al, 2007).

[edit] Mutation studies

Mutations in MYH7 are a common cause for hypertrophic cardiomyopathy (OMIM:192600) and are well recognized in dilated cardiomyopathy and left ventricle non-compaction (LVNC) (Anan R et al., 1994). Mutations in MYH7 are distributed throughout the molecule, and the relationship between mutation location, cardiomyopathy type, and disease severity is poorly understood.

External references for MYH7

• ensembl: ENSG00000092054
• OMIM: 160760
• Search miRBase for MYH7
• Expression patterns from 4DXPress: MYH7
• MGI: MGI:2155600
• ZFIN: ZDB-GENE-991123-5
• Wikipedia: MYH7
• Search Wikiproteins: MYH7
• Search Genetic Association Database: MYH7
• Search GeneTests: MYH7
• CHeartED:

Known phenotypes for MYH7

Non-syndromic

ASD

Support: likely: 2 or more patients (with CHD and a mutation in the candidate gene) References: PMID:18159245 (single case report ) Inheritence: Non-syndromic ASD in association with left ventricle non-compaction (LVNC) and Ebstein's anomaly. Incidence: Heterozygous MYH7 mutations were identified in 8 of 141 samples (6%) (Postma AV et al., 2010). Comments: Studies: (1) [ show ] [ hide ] Reference: PMID:18159245 Incidence: 4/4 patients Comments: Budde BS et al., 2007 reported on a heterozygous mutation in the MYH7 gene in a family with 9 affected members presenting left ventricle non-compaction. The mutation was exclusively present in morphologically affected family members. In addition to non-compaction of the ventricular myocardium (NVM), three individuals displayed an atrial septal defect and Ebstein’s anomaly. One patient had NVM and ASD and one patient showed NVM in combination with Ebstein's anomaly. Add another study.

Ebstein's malformation of tricuspid valve

Support: likely: 2 or more patients (with CHD and a mutation in the candidate gene) References: PMID:21127202 (population study with screening of similar CHD patients and normal controls ) PMID:18159245 (single case report ) Inheritence: Non-syndromic Ebstein anomaly in association with left ventricle non-compaction (LVNC). Incidence: Heterozygous MYH7 mutations were identified in 8 of 141 samples (6%) (Postma AV et al., 2010). Comments: Studies: (2) [ show ] [ hide ] Reference: PMID:21127202 Incidence: 8/141 patients Comments: Postma AV et al., 2010 screened for mutations in the MYH7 gene in 141 unrelated subjects with Ebstein anomaly. Seven distinct heterozygous mutations were identified in 8 of 141 samples (6%). Two of the reported mutations were known to cause hypertrophic cardiomyopathy. In 6 of 8 probands with MYH7 mutations LVNC was identified in addition to Ebstein anomaly. Reference: PMID:18159245 Incidence: 4/4 patients Comments: Budde BS et al., 2007 reported on a heterozygous mutation in the MYH7 gene in a family with 9 affected members presenting left ventricle non-compaction. The mutation was exclusively present in morphologically affected family members. In addition to non-compaction of the ventricular myocardium (NVM), three individuals displayed an atrial septal defect and Ebstein’s anomaly. One patient had NVM and ASD and one patient showed NVM in combination with Ebstein's anomaly. Add another study.

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Syndromic

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Protein interaction partners

Patients reports for MYH7

Translocations

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Mutations in MYH7

Mutation (DNA)	Mutation (peptide)	CHD	Reference	Other features	Inheritence	Additional info.
	p.1220delQ	Ebstein's malformation of tricuspid valve	PMID:21127202	Ebstein, LVNC (proband AO)	Dominant Sporadic	show hide Genetic evidence This variant was inherited from an unaffected parent. This variant was not found in 490 ethnically matched controls. in silico prediction Functional studies No functional studies were performed for this variant. Comments Further functional studies are required to assess the impact of this variant on cardiac development.
	p.1459K>N	Ebstein's malformation of tricuspid valve	PMID:21127202	Ebstein (proband AD)	Dominant Sporadic	show hide Genetic evidence This variant was inherited from an unaffected parent. This variant was not found in 490 ethnically matched controls. in silico prediction All identified missense mutations affect amino acids with high degrees of conservation throughout evolution, underscoring the functional importance of these residues. Functional studies No functional studies were performed for this variant. Comments Further functional studies are required to assess the impact of this variant on cardiac development.
	p.1573Q>K	Ebstein's malformation of tricuspid valve	PMID:21127202	Ebstein, VSD (kindred 109.787)	Dominant Sporadic	show hide Genetic evidence This variant was inherited from an unaffected father. This variant was not found in 490 ethnically matched controls. in silico prediction All identified missense mutations affect amino acids with high degrees of conservation throughout evolution, underscoring the functional importance of these residues. Functional studies This variant was inherited from an unaffected father. Comments Further functional studies are required to assess the impact of this variant on cardiac development.
	p.1918N>K	Ebstein's malformation of tricuspid valve	PMID:21127202	Ebstein, LVNC (kindred 110.240)	Dominant Familial	show hide Genetic evidence Segregating : The proband's son presented with bicuspid aortic valve, aortic coarctation, and LVNC. The proband’s asymptomatic brother had LVNC and LV dilatation with LV dysfunction; the proband's mother was also found to have LVNC. All affected family members carried the mutation. This variant was not found in 490 ethnically matched controls. in silico prediction All identified missense mutations affect amino acids with high degrees of conservation throughout evolution, underscoring the functional importance of these residues. Functional studies No functional studies were performed for this variant. Comments Further functional studies are required to assess the impact of this variant on cardiac development.
c.842G>C	p.281R>T	Ebstein's malformation of tricuspid valve	PMID:18159245	Non-compaction of the ventricular myocardium with Ebstein's anomaly and/or ASD	Dominant Familial	show hide Genetic evidence Segregating The mutation was exclusively present in morphologically affected family members. This variant was not detected in 184 normal controls. in silico prediction The p.281R>T missense mutation is located in the globular head of MHC-beta and affects a position in the vicinity of the switch I loop of the ATPase. The mutation affects a highly conserved amino acid in the myosin subfragment-1 (R281T). In silico simulations suggest that the mutation R281T prevents the formation of a salt bridge between residues R281 and D325, thereby destabilizing the myosin head (Budde BS et al., 2007). Functional studies No functional studies were performed for this variant. Comments Further functional studies are required to assess the impact of this variant on cardiac development.
	p.283Y>D	Ebstein's malformation of tricuspid valve	PMID:21127202	Ebstein, LVNC (kindred 16875)	Dominant Familial	show hide Genetic evidence Segregating : This variant was inherited from a father with LVNC. This variant was not found in 490 ethnically matched controls. in silico prediction All identified missense mutations affect amino acids with high degrees of conservation throughout evolution, underscoring the functional importance of these residues. Functional studies No functional studies were performed for this variant. Comments Further functional studies are required to assess the impact of this variant on cardiac development.
	p.283Y>D	Ebstein's malformation of tricuspid valve	PMID:21127202	Ebstein, ASD type II, LVNC (kindred 110.647)	Dominant Familial	show hide Genetic evidence Segregating : Family screening identified LVNC in a five family members. In addition, one family member presented with Ebstein's anomaly, and one with a perimembranous VSD. All affected family members carried the mutation. This variant was not found in 490 ethnically matched controls. in silico prediction All identified missense mutations affect amino acids with high degrees of conservation throughout evolution, underscoring the functional importance of these residues. Functional studies No functional studies were performed for this variant. Comments Further functional studies are required to assess the impact of this variant on cardiac development.
	p.350Y>D	Ebstein's malformation of tricuspid valve	PMID:21127202	Ebstein, biventricular non-compaction (proband DB)	Recessive Familial	show hide Genetic evidence Segregating This variant was not found in 490 ethnically matched controls. in silico prediction All identified missense mutations affect amino acids with high degrees of conservation throughout evolution, underscoring the functional importance of these residues. Functional studies No functional studies were performed for this variant. Comments Further functional studies are required to assess the impact of this variant on cardiac development.
	p.390L>P	Ebstein's malformation of tricuspid valve	PMID:21127202	Ebstein, LVNC (proband BT)	Dominant Sporadic	show hide Genetic evidence This variant was inherited from an unaffected parent. This variant was not found in 490 ethnically matched controls. in silico prediction All identified missense mutations affect amino acids with high degrees of conservation throughout evolution, underscoring the functional importance of these residues. Functional studies No functional studies were performed for this variant. Comments Further functional studies are required to assess the impact of this variant on cardiac development.

Representation of protein MYH7

Heart expression domain of MYH7

No specified expression domain for MYH7

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Associated CHDs found by automated text mining

AGeneApart Method

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Heart defects

This page contributors

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