WERNER SYNDROME - STUDIES IN AN AFFECTED FAMILY REVEAL A CELLULAR PHENOTYPE OF UNAFFECTED SIBLINGS

Werner syndrome is an inherited disease with symptoms of presenescence . The primary defect site either on the protein or at the DNA level is not known, nor is it possible to identify a heterozygous phenotype. O n the basis of cellular peculiarities expressed in the homozygotes-lif espan reduction of cells in culture; length of population doubling tim e and chromosomal instability-we searched for a 'Werner-like' phenotyp e in otherwise phenotypically unaffected siblings. We established prim ary fibroblasts from eight members of a Tyrolean family, two of whom h ad been diagnosed as typical Werner syndrome, as well as from unrelate d healthy young and old volunteers. Determination of the lifespan of e ach strain and studies on population doubling time and chromosomal ins tability revealed similar cellular characteristics in all family membe rs, albeit to a lesser extent with the siblings than with the homozygo tes when compared to age-matched controls. These features, also appare nt in cultivated fibroblasts from old but healthy controls, appear to be indicative of Werner syndrome when expressed in young or middle age d persons. The possible identification of otherwise clinically healthy gene carriers of Werner syndrome is of utmost importance for genetic counselling and medical surveillance for this disorder.