Huntington's Disease Mutation Expands Silently for Decades

Tejal Somvanshi

Scientists discovered why Huntington's disease strikes in mid-life: a genetic mutation silently grows for decades before causing brain cell death.

Photo Source: Frank Gaillard (CC BY-SA 3.0)

The mutation involves a DNA sequence (CAG) that repeats 40+ times in people with Huntington's, compared to 15-35 times in those without the disease.

Photo Source: NHGRI (CC BY-SA 3.0)

Research on brain tissue from 53 people with Huntington's and 50 without it showed the mutation grows slowly at first, then accelerates when reaching about 80 repeats.

Photo Source: ZEISS Microscope (CC BY-NC-ND 2.0)

Scientists found some striatal projection neurons, which control movement and thinking, contained up to 800 CAG repeats.

Photo Source: NIH Image Gallery (CC BY-SA 2.0)

The surprise finding: neurons remain stable with up to 150 CAG repeats, but beyond that threshold, they lose critical gene function and die.

Photo Source: Bruttokolliko (CC BY-SA 4.0)

Previous treatments targeting the mutated gene struggled because they only helped the few cells that crossed the toxic threshold.

Photo Source: Howard Vindin (CC BY-SA 4.0)

Scientists now aim to slow or stop CAG repeat expansion, potentially delaying or preventing symptoms in 41,000 affected Americans.

Photo Source: GFDL (CC BY-SA 3.0)

The research offers hope for understanding other genetic disorders with DNA repeats, like fragile X syndrome and myotonic dystrophy.

Photo Source: DennisM2 (CCO 1.0)

Brain tissue donations from Huntington's patients made this discovery possible, creating lasting knowledge that will benefit future generations.

Photo Source: Juan Carlos Fonseca Mata (CC BY-SA 4.0)

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