Juvenile Huntington's disease: does a dosage-effect pathogenic mechanism differ from the classical adult disease?
Huntington's disease (HD) is caused by a CAG repeat mutation translating as a polyglutamine (poly(Q)) expansion in the huntingtin protein, whose main pathogenic mechanism is a gain of toxic function. In the case of large expansions beyond 60 repeats onset may result in juvenile HD (JHD, onset before 20 years of age). However, the triplet number does not represent the only onset modifier even in case of large expansions, mechanisms other than the size of the mutation contribute to the phenotype. In this review we discuss the possibility that some of the pathogenic mechanisms contributing to age at onset and progression may differ in the early onset HD compared with the classical adult pathology.
Squitieri
Ferdinando
F
Neurogenetics Unit, IRCCS Neuromed, Pozzilli, IS, Italy. neurogen@neuromed.it
Frati
Luigi
L
Ciarmiello
Andrea
A
Lastoria
Secondo
S
Quarrell
Oliver
O
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000235:genetics*; D010641:Phenotype; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics*
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine