The discovery that trinucleotide repeats could expand during intergenerational transmission and could cause disease was the first evidence that not all disease-causing mutations are stably transmitted from parent to offspring.There are several known categories of trinucleotide repeat disorder. Category I includes Huntingtons disease (HD) and the spinocerebellar ataxias. These are caused by a CAG repeat expansion in protein-coding portions, or exons, of specific genes. Category II expansions are also found in exons, and tend to be more phenotypically diverse with heterogeneous expansions that are generally small in magnitude. Category III includes fragile X syndrome, myotonic dystrophy, two of the spinocerebellar ataxias, juvenile myoclonic epilepsy, and Friedreichs ataxia. These diseases are characterized by typically much larger repeat expansions than the first two groups, and the repeats are located in introns rather than exons. Types
Some of the problems in trinucleotide repeat syndromes result from causing alterations in the coding region of the gene, while others are caused by altered gene regulation. In over half of these disorders, the repeated trinucleotide, or codon, is CAG. In a coding region, CAG codes for glutamine (Q), so CAG repeats result in a polyglutamine tract. These diseases are commonly referred to as polyglutamine (or polyQ) diseases. The repeated codons in the remaining disorders do not code for glutamine, and these are classified as non-polyglutamine diseases. Polyglutamine (PolyQ) diseases
Non-polyglutamine diseases
Symptoms and signs
A common symptom of polyQ diseases is the progressive degeneration of nerve cells, usually affecting people later in life.
First arch syndromes are congenital defects caused by a failure of neural crest cells to migrate into the first pharyngeal arch. They can produce facial anomalies. Examples of first arch syndromes include Treacher Collins syndrome and Pierre Robin syndrome. == References ==