Historical perspective of defining Charcot-Marie-Tooth type 1B

A single family (1521) with CMT has been followed for 36 years (1962-1998) at Children's Hospital and the University of Washington in Seattle. The family was initially called peroneal muscular atrophy with severely slowed motor nerve conduction velocities (5-15 m/sec), In the late 1970s the family was part of several genetic studies of CMT and in 1980 represented linkage of CMT to the Duffy (Fy) locus on chromosome 1q. This finding was confirmed in an Indiana CMT family by Stebbins and Conneally (1982). This subtype of CMT was designated 1B, These investgations represented some of the last successful linkage studies in the now seemingly "ancient" pre-DNA marker era. In 1993 Hayasaka and colleagues found a point mutation in the myelin P-0 gene (Asp 90 Glu) in this family, giving CMT1B a molecular basis. The historical development of this "defining'" of a neurogenetic disorder reveals interesting insights into the workings of clinical genetics over the past 3 decades.