Adult-onset autosomal dominant leukodystrophy with autonomic symptoms restricted to 1.5 Mbp on chromosome 5q23.
Autosomal dominant leukodystrophy (ADLD) with autonomic symptoms is a slowly progressive leukodystrophy with an onset in the 4th to 6th decade of life. Early symptoms are derived from the autonomic nervous system with bladder dysfunction in the majority of patients. The disease progresses slowly with loss of fine motor skills, ataxia, and affected individuals may survive for two decades after onset of symptoms. The molecular basis behind ADLD remains unknown but the causative locus was previously mapped to a 4 cM region on chromosome 5. We have recently identified a large family of Swedish origin with this type of ADLD. Linkage analysis on samples from family members confirmed linkage to 5q23 and supports genetic homogeneity for the disease. We fine mapped and localized the ADLD gene to a 0.96 cM region between D5S1495 and CTT/CCT15. A maximum parametric multipoint location score of 9.45 was obtained for a position at the marker CTT55. From our results we conclude that the ADLD gene locus is restricted to a 1.47 Mbp interval containing 13 known or putative genes.
Marklund
Lena
L
Department of Genetics and Pathology, Clinical Molecular Genetics, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden. lena.marklund@genpat.uu.se
Melin
Malin
M
Melberg
Atle
A
Giedraitis
Vilmantas
V
Dahl
Niklas
N
D000328:Adult; D020029:Base Pairing; D001483:Base Sequence; D002895:Chromosomes, Human, Pair 5; D017931:DNA Primers; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008297:Male; D010375:Pedigree; D013106:Sphingolipidoses / Q000235:genetics*
D017931:DNA Primers