ABSTRACT
To illustrate the variable clinical presentations and rates of progression in familial hypertrophic cardiomyopathy (FHC), phenotypes and genotypes were compared in three FHC families with different genetic defects. In the first family, the FHC abnormality was a protein truncating mutation (Gln969X) in the cardiac myosin binding protein C gene. The second family had a missense change (Asn755Lys) in the same gene. A missense mutation (Arg453Cys) in the cardiac beta myosin heavy chain gene was present in the third family. Penetrance associated with the Gln969X defect was 27% in the age range 0 to 40 years. This was considerably less than the 93% penetrance (0 to 40 years) observed in the two families with missense mutations. The variable penetrance in FHC, as well as the unpredictability of sudden cardiac death, complicates clinical diagnosis and management, including genetic counselling. Although a genetic disease with a predominantly adult onset, there are counselling issues in FHC which set it aside from other adult onset disorders.
Subject(s)
Cardiomyopathy, Hypertrophic/genetics , Genetic Counseling , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Cardiomyopathy, Hypertrophic/classification , Cardiomyopathy, Hypertrophic/etiology , Child , Child, Preschool , DNA Mutational Analysis , Echocardiography , Family , Female , Genotype , Humans , Male , Middle Aged , Mutation , Pedigree , Penetrance , Phenotype , Risk AssessmentABSTRACT
DNA studies in familial hypertrophic cardiomyopathy (FHC) have shown that it is caused by mutations in genes coding for proteins which make up the muscle sarcomere. The majority of mutations in the FHC genes result from missense changes, although one of the most recent genes to be identified (cardiac myosin binding protein C gene, MYBPC3) has predominantly DNA mutations which produce truncated proteins. Both dominant negative and haploinsufficiency models have been proposed to explain the molecular changes in FHC. This study describes two Australian families with FHC caused by different mutations in MYBPC3. The first produces a de novo Asn755Lys change in a cardiac specific domain of MYBPC3. The second is a Gln969X nonsense mutation which results in a truncated protein. Neither mutation has previously been found in the MYBPC3 gene. The consequences of DNA changes on the function of cardiac myosin binding protein C are discussed in relation to current molecular models for this disorder.
Subject(s)
Cardiomyopathy, Hypertrophic/genetics , Cardiomyopathy, Hypertrophic/pathology , Carrier Proteins/genetics , Myosins/metabolism , Amino Acid Sequence , Australia , Carrier Proteins/chemistry , DNA Mutational Analysis , Female , Genetic Linkage , Haplotypes , Humans , Male , Middle Aged , Molecular Sequence Data , Mutation , Pedigree , Protein Conformation , Structure-Activity RelationshipABSTRACT
Experiences with a training programme in intensive care in a country hospital are described. Difficulties in getting adequate numbers of trained persons to act as instructors can be partially overcome by the use of recorded tapes and manikins. The benefits of such a programme make it a worth-while venture for any similar unit.
Subject(s)
Critical Care , Education, Nursing, Continuing , Hospitals, General , AustraliaABSTRACT
A 24-year-old multipara 34 weeks pregnant presented in shock due to massive pulmonary embolism. Recovery followed thrombolytic therapy, although fetal death occurred early. There were no serious maternal side effects, although hypofibrinogenaemia occurred. Thrombolytic therapy is considered to offer advantages over heparin in this situation.
