Trinucleotide repeat expansions

Expanded trinucleotide repeat regions represent new, unstable
mutations that were identified in 1991. This type of mutation is
the cause of several major genetic disorders, including fragile
X syndrome, myotonic dystrophy, Huntington disease,
spinocerebellar ataxia and Friedreich ataxia. In the normal
copies of these genes the number of repeats of the
trinucleotide sequence is variable. In affected individuals the
number of repeats expands outside the normal range. In
Huntington disease the expansion is small, involving a
doubling of the number of repeats from 20–35 in the
normal population to 40–80 in affected individuals. In fragile
X syndrome and myotonic dystrophy the expansion may be
very large, and the size of the expansion is often very unstable
when transmitted from affected parent to child. Severity of
these disorders correlates broadly with the size of the
expansion: larger expansions causing more severe disease.