The initial ALS4 Diagnosis - 1998
Linkage of the gene for an autosomal dominant form of juvenile amyotrophic lateral sclerosis to chromosome 9q34.
Published: Am J Hum Genet. 1998 Mar; 62(3): 633–640. DOI: 10.1086/301769. PMCID: PMC1376963. Authors: Phillip F. Chance, Bruce A. Rabin, S G Ryan, Y Ding, M Scavina, B Crain, John W. Griffin, and David R. Cornblath.
Link to article: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1376963/
We performed genetic mapping studies of an 11-generation pedigree with an autosomal dominant, juvenile-onset motor-systems disease. The disorder is characterized by slow progression, distal limb amyotrophy, and pyramidal tract signs associated with severe loss of motor neurons in the brain stem and spinal cord. The gene for this disorder, classified as a form of juvenile amyotrophic lateral sclerosis (ALS), is designated "ALS4." We performed a genomewide search and detected strong evidence for linkage of the ALS4 locus to markers from chromosome 9q34. The highest LOD score (Z) was obtained with D9S1847 (Z=18.8, recombination fraction of .00). An analysis of recombinant events identified D9S1831 and D9S164 as flanking markers, on chromosome 9q34, that define an approximately 5-cM interval that harbors the ALS4 gene. These results extend the degree of heterogeneity within familial ALS syndromes, and they implicate a gene on chromosome 9q34 as critical for motor-neuron function.