Gene "MYOZ2"
Found 1 record
Gene information
Gene symbol:
MYOZ2
See related:
Ensembl: ENSG00000172399, Gene ID: 51778
Additive variants :
Undetected
Genetic interaction partners
No data
Modifier statisitcs
Record:
1 
Disorder:
1 
Vriant:
1 
Reference:
1 
Effect type:
Expressivity(1)  
Modifier effect:
Altered onset time and altered severity(1)  
Detail：
  • Variant 1:
    MYOZ2:c.505A-C(p.L169G)
    Gene:
    MYOZ2
    Genomic location:
    dbSNP ID:
    Target disease:
    Hypertrophic Cardiomyopathy(DOID_11984)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered onset time and altered severity 
    Evidence:
    Pedigree analysis 
    Effect:
    The MYOZ2-L169G mutation alone was not found to be pathogenic, but it did appear to play a modifying role in HCM.
    Reference:
    PMID28296734
    Title:
    Genetic anticipation in a special form of hypertrophic cardiomyopathy with sudden cardiac death in a family with 74 members across 5 generations.
    Species studied:
    Human
    Abstract:
    Hypertrophic cardiomyopathy (HCM) is the most common heritable heart disease. The genetic anticipation of HCM and its associated etiology, sudden cardiac death (SCD), remains unclear. The aim of this study was to investigate the mechanism underlying the genetic anticipation of HCM and associated SCD.An HCM family including 5 generations and 74 members was studied. Two-dimensional echocardiography was performed to diagnose HCM. The age of onset of HCM was defined as the age at first diagnosis according to hospital records. The information on SCD was confirmed by verification by ≥2 family members and a review of hospital records. Whole-genome sequencing was performed on 4 HCM subjects and 1 healthy control in the family. The identified mutations were screened in all available family members and 216 unrelated healthy controls by Sanger sequencing.The median ages of onset of HCM were 63.5, 38.5, and 18.0 years in members of the second, third, and fourth generations of the family, respectively, and the differences between the generations were significant (P<0.001). The age at SCD also decreased with each subsequent generation (P<0.05). In particular, among the third-generation family members, SCD occurred between 30 and 40 years of age at approximately 8 AM, whereas among the fourth-generation family members, all 5 males who experienced SCD were 16 years of age and died at approximately 8 AM. The sarcomere gene mutations MYH7-A719H and MYOZ2-L169G were detected in the HCM individuals in this pedigree. Increases in the number of mutations and the frequency of multiple gene mutations were observed in the younger generations. Moreover, a structural variant was present in the HCM phenotype-positive subjects but was absent in the HCM phenotype-negative subjects.HCM may exhibit genetic anticipation, with a decreased age of onset and increased severity in successive generations. Multiple gene mutations may contribute to genetic anticipation in HCM and thus may be of prognostic value.