Melecular genetic study in the pathogenesis of achondroplasia

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We developed a rapid and reproducible method of two-dimensional electrophoresis for screening of abnormal proteins expressed in fibroblasts from patients with inherited diseases. After silver staining, the electrophoresis gel was subjected to semi-automatic digitizer-personal computer analysis. It was used for detection of abnormal spots in inherited diseases of currently unknown etiology. In a preliminary study, some patients with achondroplasia showed two abnormal spots that were not detected in inherited other individuals, healthy or with other metabolic/nonmetabolic diseases. However, after a survey of a large number of cell strains, we found that they are not specific of achondroplasia but expressed in some individuals not related to this disease. They may represent neutral polymorphism or have connection to specific physical condition. We have not further information about their physiological roles as yet.Simulteneously, in addition to streening of abnormal protein expressio in diseases, we did analysis of proteins expressed by mutant genes responsible for inherited lysosomal diseases. Each mutant gene expressed different intracellular turnover of mutant proteins in human beta-galactosidase deficiency diseases, and a clear relation between phenotype and genotype was observed in human beta-galactosidase deficiency diseases.