Three novel 63 cardiac myosin heavy chain (MHC) gene missense mutations, Phe513Cys, Gly716Arg, and Arg719Trp, which cause familial hypertrophic cardiomyopathy (FHC) are described. One mutation in exon 15 (Phe513Cys) does not alter the charge of the encoded amino acid, and affected family members have a near normal life expectancy. The Gly716Arg mutation (exon 19; charge change of +1) causes FHC in three family members, one of whom underwent transplantation for heart failure. The Arg719Trp mutation (exon 19; charge change of -1) was found in four unrelated FHC families with a high incidence of premature death and an average life expectancy in affected individuals of 38 yr. A comparable high frequency of disease-related deaths in four families with the Arg719Trp mutation suggests that this specific gene defect directly accounts for the observed malignant phenotype. Further, the significantly different life expectancies associated with the Arg719Trp vs. Phe513Cys mutation (P < 0.001) support the hypothesis that mutations which alter the charge of the encoded amino acid affect survival more significantly than those that produce a conservative amino acid change. (J. Clin. Invest. 1994. 93:280-285.)

a b s t r a c tWe focus on the zero-catch problem of CPUE (catch per unit effort) standardization. Because the traditional CPUE model with a log-normal error structure cannot be applied in this case, three methods have often been utilized as follows:(1) Ad hoc method adds a small constant value to all response variables.(2) Catch model with a Poisson or negative-binomial (NB) error structure. (3) Delta-type two-step method such as the delta-normal model (after estimating the ratio of zero-catch using a logit or probit model, a model such as CPUE log-normal or Catch-Poisson is applied to CPUE without zero-data).However, there are some statistical problems with each of these methods.In this paper, we carried out the CPUE standardization mainly using the Tweedie distribution model based on the actual by-catch data (silky shark, Carcharhimus falciformis, in the North Pacific Ocean caught by Japanese training vessels) including many observations with zero-catch (>2/3rd) and tuna fishery data as a target (yellowfin tuna, Thunnus albacares, in the Indian Ocean caught by Japanese commercial vessels) where the ratio of zero-catch is not so high (<1/3rd). The Tweedie model is an extension of compound Poisson model derived from the stochastic process where the weight of the counted objects (i.e., number of fish) has a gamma distribution and has an advantage of handling the zero-catch data in a unified way.We also compared four candidate models, the Catch-NB model, ad hoc method, Delta-lognormal model (delta-type two-step method) and Tweedie distribution, through CPUE analyses of actual fishery data in terms of the statistical performance. Square error and Pearson's correlation coefficient were calculated based on the observed CPUE and the corresponding predicted CPUE using the n-fold cross-validation.As a result, the differences in the trend of CPUE between years and model performance between the ad hoc method and Tweedie model were found to be not so large in the example of yellowfin tuna (target species). However, the statistical performance of Tweedie distribution is rather better than Deltalognormal model, the Catch-NB distribution and ad hoc method in the example of silky shark (by-catch species). Standardized CPUE year trend of ad hoc method was found to be quite different from that of the Tweedie distribution and other two models. Model performance of the Tweedie distribution is good judging from the 5-fold cross-validation using the fishery data if including many zero-catch data such as by-catch species.

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Background —Mutations that cause familial hypertrophic cardiomyopathy have been identified in several genes that encode contractile proteins. Patients with mutations in the cardiac troponin T (cTnT) gene have particularly poor prognosis but only mild hypertrophy. To date, no benign mutation in the cTnT gene has been reported. The clinical characteristics and prognosis of patients with the Phe110Ile mutation in the cTnT gene is unclear because few affected individuals have been identified. Methods and Results —Forty-six probands with familial hypertrophic cardiomyopathy were screened for mutations in the cTnT gene. The Phe110Ile missense mutation was found in 6 probands. Individuals in the 6 families were analyzed genetically and clinically. Haplotype analysis was performed with markers encompassing the cTnT gene. Left ventricular hypertrophy was classified as type I, II, III, or IV according to the criteria of Maron et al. The Phe110Ile mutation in the cTnT gene was identified in 16 individuals. Two of the 6 families shared the same flanking haplotype, and 4 were different from each other. Affected individuals exhibited different cardiac morphologies: 4 had type II, 6 had type III, and 3 had type IV hypertrophy with apical involvement. Three individuals with the disease-causing mutation did not fulfill clinical criteria for the disease. The product-limit survival curve analysis demonstrated a favorable prognosis. Conclusions —Multiple independent mutations of residue 340 in the cTnT gene have been described, suggesting that this may be a “hot spot” for such events. The Phe110Ile substitution causes hypertrophic cardiomyopathy with variable cardiac morphologies and a favorable prognosis.