Question

Develop a case study/report on the Huntington disease and the gene for this disease is HTT gene. When you are developing the case study, start it from the DNA variant(a specific variant of the HTT gene) to the phenotype of the diseased patient.

The case report you should include the following:

1) If the gene exonic, type of variant (SNP of CNV) and resultant changes in protein or protein level.

2) Is the variant found in the non-coding region and if it involved in transcriptional regulation, and describe the proposed pathway.

3) Draw a three-generation pedigree with at least 15 family members.

4) A narrative describing the pedigree of the disease.

Answer 1

• Huntington's disease is a dominantly inherited disorder in which all affected individuals have precisely disorder in which all affected individuals have precisely the same type of mutation, the expansion of a normally polymorphic CAG trinucleotide repeat in the HD gene, which lengthens a variable polyglutamine tract in the huntingtin protein.
• Within a year after the identification of the HD mutation, the inverse relationship between CAG length and age at diagnostic motor onset, which lay the foundation for a genetic driven approach to understanding.
• Huntington's disease is an autosomal dominant neurodegenerative disorder that affects approximately 5-10 individuals per 100,100. Mutant huntingtin is highly aggregation prone an the formation of cytoplasmic aggregates and nuclear inclusions throughout the brain is one of the most striking hallmarks of HD.
• HD is one of nine inherited neurodegenerative disorder caused by an expansion of glutamine residue in the causative protein, the order being spinocerebellar ataxis. Toxicity in these disorders stems primarily from a gain of function conferred by the polyglutamine stretch, the pathogenic length of which is disease specific.
• The expression of genes important for calcium homeostasis, neuronal differentiation, neuronal survival and neurotransmission are reduced early in HD.