G2Cdb::Allele report

Mutation type
N

Altered genes (1)

Gene Symbol Species Description
G00002430 MYH6 Homo sapiens myosin, heavy chain 6, cardiac muscle, alpha

Diseases (1)

Disease Description Nervous effect
D00000235 Hypertrophic cardiomyopathy N

Literature (1)

Pubmed - human_disease

  • Myozenin 2 is a novel gene for human hypertrophic cardiomyopathy.

    Osio A, Tan L, Chen SN, Lombardi R, Nagueh SF, Shete S, Roberts R, Willerson JT and Marian AJ

    Center for Cardiovascular Genetic Research, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Sciences Center, Houston, TX 77030, USA.

    Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in sarcomeric proteins (excluding phenocopy). The causal genes in approximately one-third of the cases remain unknown. We identified a family comprised of 6 clinically affected members. The phenotype was characterized by early onset of symptoms, pronounced cardiac hypertrophy, and cardiac arrhythmias. We excluded MYH7, MYBPC3, TNNT2, and ACTC1 as the causal gene either by direct sequencing or by haplotype analysis. To map the putative candidate sarcomeric gene, we perforbold locus-specific haplotyping to detect cosegregation of the locus haplotype with the phenotype, followed by mutation screening. We genotyped 5 short-tandem-repeat markers that spanned a 4.4-centimorgan region on 4q26-q27 locus and encompassed myozenin 2 (MYOZ2), a Z-disk protein. The maximum logarithm of odds score was 2.03 (P=0.005). All affected members shared a common haplotype, implicating MYOZ2 as the causal gene. To detect the causal mutation, we sequenced all exons and exon-intron boundaries of MYOZ2 in 10 family members and identified a T-->C missense mutation corresponding to S48P substitution, which cosegregated with inheritance of HCM (N=6). It was absent in 4 clinically normal family members and in 658 additional normal individuals. To determine frequency of the MYOZ2 mutations in HCM, we sequenced MYOZ2 in 516 HCM probands and detected another missense mutation (I246M). It was absent in 2 normal family members and 517 controls. Both mutations affect highly conserved amino acids. We conclude MYOZ2 is a novel causal gene for human HCM.

    Funded by: NHLBI NIH HHS: P50 HL054313, P50 HL054313-060012, P50 HL054313-070012, P50 HL054313-080012, P50 HL054313-08S10012, P50 HL054313-090012, P50 HL054313-100012, R01 HL068884, R01 HL068884-01, R01 HL068884-02, R01 HL068884-03, R01 HL068884-04, R01 HL068884-05, R01-HL68884

    Circulation research 2007;100;6;766-8

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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