Trinucleotide Repeat Expansion Disorders

Question 1

<p>Fragile X Syndrome</p>

Answer 1

<p>Associated with a triplet repeat (CGG) expansion in the noncoding region 5' to the fragile X mental retardation gene, FMR-1. >2000 repeats. Also results in methylation of the region and transcriptional shut-down of FMR-1. Observed by karyotyping, PCR and southern blot (best). Severity increases with generations.</p>

Question 2

<p class=”large” style=”text-align:center”;>Huntington’s Disease</p>

Answer 2

<p class=”large” style=”text-align:center”;>Characterized by expansion within coding sequence of Huntingtin structural gene (4p16.3). Repeat CAG expands from 9-37 repeats to 38-86 inserting multiple glutamine residues at 5’ end of protein (causes protein to aggregate in plaques, esp in nervous tissue). Detectable by PCR. Child has 50% chance of inheriting. </p>

Question 3

<p>Idiopathic Congential Central Hypoventilation Syndrome (CCHS)</p>

Answer 3

<p>A rare pediatric disorder characterized by inadequate breathing while asleep. Occurs in association with intestinal disorder called Hirschsprung's disease and symptoms of diffuse autonomic nervous system dyregulation/dysfunction. Many gene mutations observed; polyalanine expansion of the paired-like homeobox (PHOX2b) gene (4p12)13. Triplet repeat expansion occurs inside PHOX2b gene resulting in insertion of multiple alanine residues into protein. More repeats - inc severity. Detected by PCR. </p>