23 October 1998

I have a pedigree of an American midwestern family with adult onset weakness in the extremities (beginning  typically in hands, progressing to feet, legs, respiratory, etc until death ). age of onset: 27-32 yrs; age of death: variable (can be over 60 yrs)

It has been suggested (by family physician?) that this represents an uncharacterized anterior horn cell degeneration. Mode of inheritance is classical autosomal dominant with full penetrance. I have DNA (periph blood) on all but 1 proband (6/7), and on several other family members (not the younger, presymptomatic generation, although I believe they are willing
to cooperate in a study). Currently, there are 3 generations living, however, the remaining proband in the grandparental generation is not expected to live much longer. I am trying to arrange an autopsy, and will bank as much nerve, brain and muscle as possible. Is anyone looking at pedigrees like this? Particularly, is anyone doing a linkage/positional
cloning project?