Trinucleotide Repeat Disease  SCA3 belongs to a class of genetic disorders called trinucleotide repeat diseases. For someone with SCA3, there are extra copies of a series of nucleotides identified by the letters C-A-G within their DNA located on chromosome 14 (14q32.1). This causes the production of a mutated protein called ataxin-3 (see Figure F-12).The protein proves to be insoluble, and accumulates in the nucleus, and interferes with its normal operation causing the cell to deteriorate and die. Autosomal Dominant SCA3 is an autosomal dominant disease, which means that only one copy of the defective gene is needed to inherit SCA3. This is unusual because most genetic disorders are recessive, meaning that in order to inherit the symptoms you would need two copies of the defective gene. Both male and female individuals are equally likely to inherit the gene and develop the disease. It passes directly from one generation to the next without skipping. Individuals who escape the disease will not pass it on to future generations. People with a defective gene have a 50% chance of passing it on to each of their children. A procedure called PGD is now available to test for SCA3 in early-stage embryos produced through in vitro fertilization (IVF). Prospective parents can request that only embryos free of the condition be implanted in a woman's uterus and allowed to develop into a child. Anticipation Anticipation sometimes occurs in SCA3 as well as in many other trinucleotide repeat diseases. It is a phenomenon in which children of affected parents develop symptoms much faster and earlier with increased severity than that of the parent. This occurs because the repeat mutation tends to expand as the genetic material is passed on from one generation to the next. There is a loose correlation between the repeat number, the age of onset, and the severity of the symptoms. However, it is impossible to predict the timing and severity of the symptoms with just the repeat count alone. On average: longer repeat length = earlier onset = more severe symptoms Link to the main page