The expanded CAG repeat associated with juvenile Huntington disease shows a common origin of most or all neurons and glia in human cerebrum.
We have analyzed the size of the expanded poly(CAG) associated with juvenile Huntington disease in the cerebra and the cerebella of five patients. The expanded poly(CAG) was always longer in the cerebrum than in the cerebellum, but the difference in size varied from patient to patient. Except for one patient who possessed an unusually large expansion, very little heterogeneity of size was detected within the cerebrum or within the cerebellum. The larger size of the expanded poly(CAG) in cerebrum must therefore have resulted from a single expansion event that took place early in cerebral development. In both cerebrum and cerebellum, the size of the expanded allele of gray matter was identical to that of white matter. We conclude that most if not all neurons and glia of cerebrum are descended from a common bipotent precursor, which segregated early in neurogenesis from the lineage leading to cerebellar neurons and glia.
Kahlem
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CNRS-UPR 2228, Régulation de la Transcription et Maladies Génétiques, UFR Biomédicale, 45, rue des Saints-Pères, 75270 Cedex 06, Paris, France.
Djian
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P
D000293:Adolescent; D000328:Adult; D000483:Alleles; D015139:Blotting, Southern; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology; D008297:Male; D009030:Mosaicism; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid