|Budget Amount *help
¥5,900,000 (Direct Cost : ¥5,900,000)
Fiscal Year 1992 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1991 : ¥1,500,000 (Direct Cost : ¥1,500,000)
Fiscal Year 1990 : ¥3,700,000 (Direct Cost : ¥3,700,000)
A novel form of angiokeratoma corporis diffusum was discovered in a Japanese female. Abnormal metabolites were detected in the patient's urine and those were reveald to be O-limked glycoaminoacids. From these chemical formula, this novel lysosomal storage disease, now termed Kanzaki disease, was revealed to be caused by an enzyme deficit, ie, alpha-N-acetylgalactosaminidase. ALL these were elucidated in the past a few years in this project. We tried to elucidate a possible defect in the gene encoding this enzyme protein in the last one year.
As a result, it was found that a base at the 985th was switched C to T resulting in a change of amino acid of arginine to tryptophane at 329th. This gene was transfected to COS-1 cell and a new protein was observed to be produced by COS-1 cell. This protein reacted with an antibody to the enzyme but did not show an enzymatic activity. Secondly, a computer-assisted two-dimensional molecular structure was studied and it showed that an change of amino acid induced a secondary change from beta-pleated sheet to random coil. this was quit different from the change observed in Schindler disease, i,e., alpha-helix formation. This change was thought to be the cause of susceptibility of these resultant abnormal enzyme proteines to proteases in lysosomes. This will explain the great differences in the phenotypical expression in the patients with Kanzaki disease and Schindler disease (Wang, A,M. Kanzaki, T. and Desnick,R.J.). These results obtained in this year will be published in Archives of Dermatology (in press,1993) and were submitted to other journals.
Thus, all research works, from the discovery to the molecular analysis of a noval lysosomal storase disease with angiokeratoma corporis diffusum (Kanzaki), planned in this project were successfully accomplished in these years.