Source: Genomics & Genetics Weekly via NewsRx.com & NewsRx.net
October 29, 2004
p. 148
(Originally reported in Lancet)
HEADLINE: PARKINSON DISEASE;
Researchers find genetic duplication causes familial Parkinson disease
A team of American and French researchers has discovered that
duplication of
the alpha-synuclein gene causes Parkinson disease in a French family.
In affected individuals, age of onset, symptoms and symptom
progression are
similar to that observed in people with sporadic or unexplained cases of
Parkinson disease. The findings, reported in the Lancet, suggest a direct
relationship between the amount of alpha-synuclein produced, the onset of
Parkinson disease, its severity and progression.
The research was led by Matthew Farrer, PhD (Morris K. Udall
Parkinson
Disease Research Center of Excellence at Mayo Clinic, Jacksonville,
Florida),
Marie-Christine Chartier-Harlin, PhD, and Alain Destee, MD (Department of
Neurology and INSERM, Lille, France).
Point mutations in the alpha-synuclein gene have previously been
linked to
the development of familial forms of Parkinson disease. This led to the
discovery that the encoded protein is a major component of Lewy bodies,
the
cellular inclusions in surviving brain cells. Lewy bodies are the key
pathologic
hallmark of sporadic Parkinson disease and related disorders, including
dementia
with Lewy bodies, multiple system atrophy and neurodegeneration with
brain iron
accumulation.
Last year, in two additional families, Farrer's group discovered that
triplication of the alpha-synuclein gene results in a devastating form of
Parkinson. Afflicted members exhibit an earlier onset disease, which
rapidly
progresses, and they exhibit subsequent cognitive decline and dementia.
"In contrast," Farrer says, "when our team of researchers looked at
afflicted individuals in our French family who have an alpha-synuclein
duplication, their disease onset was later, the progression of disease
was
slower and cognitive decline and dementia weren't prominent. The findings
provide convincing evidence that the amount of alpha-synuclein expressed,
or
present, in the human brain influences the disease course."
Of note, Farrer's group and others have previously shown that common
variation within the alpha-synuclein promoter sequence, an area of DNA
upstream
of the coding gene that is responsible for its expression, is associated
with
susceptibility to sporadic Parkinson disease.
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