Amish, Mennonite, and Hutterite
Genetic Disorder Database

Cardiomyopathy, familial hypertropic, 4

Disorder
OMIM #: #115197  (Click to access OMIM database)
Disorder: Cardiomyopathy, familial hypertropic, 4 
Also known as: CMH4 
Clinical
Phenotype: hypertropic cardiomyopathy, reduced systolic function, pericardial effusion, cardiomegaly, thickened septum, other cardiac irregularities, arrhythmia, syncope, stroke, heart failure, sudden death 
Seen In: Amish
Old Order Mennonite
Old Colony Mennonite
Unknown/Other Mennonite
Hutterite
Remarks: Autosomal dominant (incomplete penetrance) 
Mutations
1   Old Colony Mennonite  
Gene: MYBPC3
Base Change: c.2373dupG
Amino Acid Change: p.Trp792Valfs*41
2   Amish, Old Order Mennonite  
Gene: MYBPC3
Base Change: c.3330+2T>G
Amino Acid Change: p.Asp1064Glyfs*38
Last updated: 2022-11-03 

References
Lynch MT, Maloney KA, Pollin TI, Streeten EA, Xu H; Regeneron Genetics Center, Shuldiner AR, Van Hout CV, Gonzaga-Jauregui C, Mitchell BD. (2021) The burden of pathogenic variants in clinically actionable genes in a founder population. Am J Med Genet A Nov;185(11):3476-3484.
PubMed ID: 34467620 
Niimura H, Bachinski LL, Sangwatanaroj S, Watkins H, Chudley AE, McKenna W, Kristinsson A, Roberts R, Sole M, Maron BJ, Seidman JG, Seidman CE. (1998) Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy. N Engl J Med 338(18):1248-57.
PubMed ID: 9562578 
Orton NC, Innes AM, Chudley AE, Bech-Hansen NT. (2008) Unique disease heritage of the Dutch-German Mennonite population. Am J Med Genet A 146A(8):1072-87.
PubMed ID: 18348259 
Redin C, Pavlidou DC, Bhuiyan Z, Porretta AP, Monney P, Bedoni N, Maurer F, Sekarski N, Atallah I, Émeline D, Jeanrenaud X, Pruvot E, Fellay J, Superti-Furga A. (2022) The Amish NM_000256.3:c.3330+2T>G splice variant in MYBPC3 associated with hypertrophic cardiomyopathy is an ancient Swiss mutation. Eur J Med Genet Sep 23:104627.
PubMed ID: 36162733 
Xin B, Puffenberger E, Tumbush J, Bockoven JR, Wang H. (2007) Homozygosity for a novel splice site mutation in the cardiac myosin-binding protein C gene causes severe neonatal hypertrophic cardiomyopathy. Am J Med Genet A 143A(22):2662-7.
PubMed ID: 17937428 
Zahka K, Kalidas K, Simpson MA, Cross H, Keller BB, Galambos C, Gurtz K, Patton MA, Crosby AH. (2008) Homozygous mutation of MYBPC3 associated with severe infantile hypertrophic cardiomyopathy at high frequency among the Amish. Heart Oct;94(10):1326-30.
PubMed ID: 18467358 

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