A genetical analysis of thirty families with Wilson's disease (hepatolenticular degeneration)

Abstract

Summary: A genetical analysis has been carried out on thirty‐two patients with Wilson's disease from thirty families obtained largely from the New York area. Fourteen of the thirty‐two patients (43.75 %) were of eastern European origin (Jews) and eight (25.0 %) came from the Mediterranean (non‐Jews); both groups came from geographically circumscribed areas.A number of differences were observed between the patients who were Jews from eastern Europe and the Mediterranean and other groups. The Jews, on an average, tended to have more consanguinity, a later onset of the disease and, consequently, a relatively increased fertility. Clinically there was no predilection for either group to have a particular type of the disease. The Jewish group of patients had an increased variance in the serum copper and ceruloplasmin levels relative to the Mediterranean group. The patients with a normal level of ceruloplasmin came from the eastern Jewish group.Not all these differences were significant statistically and collection of more cases will be needed before firm conclusions can be drawn. The possibility that the eastern European Jewish population may possess a modifying gene and the possibility that more than one allele is present at the Wilson's disease locus is discussed.It should be emphasized that the evidence available is insufficient to state that ceruloplasmin is the primary gene product in Wilson's disease. If further evidence lends support to this view it will be necessary to perform structural studies on ceruloplasmin obtained from patients with Wilson's disease of various geographic origins in order to investigate the possibility of chemical allelism.This manuscript was written during the tenure of the position of Honorary Research Assistant at the Galton Laboratory, London. I am very much indebted to Prof. L. S. Penrose for his constant advice and for his critical reading of the manuscript.