Triplet Repeat Mutations

TRIPLET REPEAT MUTATIONS

Fragile X syndrome is due to triplet nucleotide repeat mutations so that the nucleotide sequence CGG repeats typically hundreds to thousands of times. The mutation occurs in the FMR-1 gene (fragile X mental retardation-1) on the X chromosome (Xq27.3), and the disease behaves as an X-linked dominant disease that causes intellectual disability in all affected males and 50% of female carriers. The characteristic phenotype includes elongated face with a large jaw, large everted ears, and macroorchidism. The condition can be diagnosed with DNA probe analysis.

Huntington disease is due to a triplet repeat mutation (CAG) of theHTTgene thatproduces an abnormal protein (huntingtin), which is neurotoxic and causes atrophy of the caudate nucleus. Huntington disease has an early onset (age range: 20–50 years) of progressive dementia with choreiform movements.