User:Jamiesherrington/Sandbox

= Huntington's disease = chorea

Aetiology
Mutation

Chromosome 4, p16.3 The huntingtin gene (HTT) protein product=huntingtin (Htt) wild type contains high polymorphic cag nucleotide repeats in the first exon to the 5' end. Disease occurs due to expansion of the cag repeats in this exon the wild type contains 10-26 repeats,28-35 intemediate (unaffected) 36-40 reduced penetrance /- affected mutant alleles contain >40 affected.

A possible cause is slippage of DNA-polymerase during spermatogenisis 3% de novo, 97% inherited. Within cells, huntingtin may be involved in signalling, transporting materials, binding proteins and other structures, and protecting against programmed cell death, the mutated form is cleaved by caspases, which creates a toxic product that kills cells, the cag repeats promote abnormal agrications of huntingtin near the nuclei of the neurons, mainly in the corpus striatum. The frequency of slippage in higher in meiosis I on the paternal side (the father)

Inheritance

The gene causing Huntington's disease is autosomal dominant, this means that mutant allele (H) masks the effect of the wild type allele (h). Therefore the phenotypes look like this As the HTT gene is on chromosome 4 the inheritance is not determined by sex, however individuals inheriting the mutation from their father have a greater risk of early onset of the disease, approximately 80% of patients with juvenile-onset Huntington's disease inherit the mutant Hd gene from their father. 97% of Huntington's disease suffers have inherited the mutant gene. Due to the dominance of the mutant allele (H) if one parent is heterozygous for the huntingtin gene (Hh) and therefore is affect by the disease each child has 50% chance of inheriting the disease. If looking at a pedigree for huntington's, the disease with not skip a generation (unless there is incomplete penetrance) Describe pedigree HH Hh hh etc Thus if one parent has Huntington's (Hh) risk for siblings.
 * Hh= Affected
 * hh= Unaffected
 * HH= Affected but very rare

Frequency

3-7/100000 w euro 0.1-0.38/100000 japs

1/10-20000 Caucasians

Phenotype
arise 30-45, but can be as early as 2 Diagnosis

Management
cure?