title: Gene mutations in apical hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Nonobstructive hypertrophy localized to the cardiac apex is an uncommon morphological variant of hypertrophic cardiomyopathy (HCM) that often is further distinguished by distinct giant negative T waves and a benign clinical course. The genetic relationship between HCM with typical hypertrophic morphology versus isolated apical hypertrophy is incompletely understood.
  
  
  RESULTS
  Genetic cause was investigated in 15 probands with apical hypertrophy by DNA sequence analyses of 9 sarcomere protein genes and 3 other genes (GLA, PRKAG2, and LAMP2) implicated in idiopathic cardiac hypertrophy. Six sarcomere gene mutations were found in 7 samples; no samples contained mutations in GLA, PRKAG2, or LAMP2. Clinical evaluations demonstrated familial apical HCM in 4 probands, and in 3 probands disease-causing mutations were identified. Two families shared a cardiac actin Glu101Lys missense mutation; all members of both families with clinical manifestations of HCM (n=16) had apical hypertrophy. An essential light chain missense mutation Met149Val caused apical or midventricular segment HCM in another proband and 5 family members, but 6 other affected relatives had typical HCM morphologies. No other sarcomere gene mutations identified in the remaining probands caused apical HCM in other family members.
  
  
  CONCLUSIONS
  Sarcomere protein gene mutations that cause apical hypertrophy rather than more common HCM morphologies reflect interactions among genetic etiology, background modifier genes, and/or hemodynamic factors. Only a limited number of sarcomere gene defects (eg, cardiac actin Glu101Lys) consistently produce apical HCM.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Arad
authors.forename: Manual
authors.initials: M
authors.lastname: Penas-Lado
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monserrat
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Maron
authors.forename: Mark
authors.initials: M
authors.lastname: Sherrid
authors.forename: Carolyn Y
authors.initials: CY
authors.lastname: Ho
authors.forename: Scott
authors.initials: S
authors.lastname: Barr
authors.forename: Ahmad
authors.initials: A
authors.lastname: Karim
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Olson
authors.forename: Mitsohiro
authors.initials: M
authors.lastname: Kamisago
authors.forename: J G
authors.initials: JG
authors.lastname: Seidman
authors.forename: Christine E
authors.initials: CE
authors.lastname: Seidman
mesh_terms: D000328:Adult; D000368:Aged; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D004452:Echocardiography; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics; D012189:Retrospective Studies; D012518:Sarcomeres / Q000235:genetics; D020107:Troponin T / Q000235:genetics; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D004247:DNA; D009124:Muscle Proteins; D018995:Myosin Heavy Chains; D020107:Troponin T; D000099163:Myosin Binding Protein C