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) the Genomic coordinates of the variant of the disease.

2) Transcript level coordinates of the variant if within mRNA (immature or mature)

2a) 5’-UTR, 3’, intron, exon, or splice site as examples

2b) If exonic, type of variant (SNP of CNV) and resultant changes in protein or protein level.

3) If the variant is in the non-coding region and if it involved in transcriptional regulation, and describe the proposed pathway.

4) Molecular mechanism of variant involved in the causing disease.

4a) Protein, transcript, and/or cellular processes disrupted

5) Transmission pattern(how is the disease transmitted to the next person).

6) Phenotypic characterization of the disease.

7) Description of genomic/epigenomic/cytogenetic/transcriptomic/proteomic characterization/detection of disease (how is the genetic cause determined)

8) Give a flow chart for determination of the genetic cause at the clinical level (i.e. phenomic upon the first presentation to the clinic to confirmation of genetic disorder).

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

10) A narrative describing the pedigree of the disease.

Answer 1

1. The huntingtin gene, also called the HTT or HD (Huntington disease) gene, is the IT15 ("interesting transcript 15") gene. The corresponding gene was predicted to encode a 3,144-residue protein with a molecular mass of 348 kD. This protein is called the huntingtin protein.

4. The Huntington disease is caused by an autosomal dominant mutation in either of an individual's two copies of a gene called huntingtin (HTT). This means a child of an affected person typically has a 50% chance of inheriting the Huntington disease. The HTT gene provides the genetic information for a protein that is also called huntingtin. HD is typically inherited, although up to 10% of cases are due to a new mutation. HTT is expressed in almost all cells. The highest concentrations of HTT are found in the brain and testes, with moderate amounts in the liver, heart, and lungs. HD is caused by an expanded CAG repeat in the gene that encodes the protein huntingtin on chromosome 4; this results in progressive atrophy of the striatum as well as cortical and other extrastriatal structures.

5. The Huntington disease is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause this disease. An affected person usually inherits the altered gene from one affected parent.

If a parent has the Huntington's disease gene, there's a:

• 50% chance of each of their children developing the disease – affected children are also able to pass the gene to any children they have.
• 50% chance of each of their children never developing the disease – unaffected children can't pass the condition on to any children they have.

6. Phenotypic characteristics of Huntington's disease are following,

movement disorders

• Involuntary jerking or writhing movements (chorea)
• Impaired gait, posture and balance.
• Muscle problems, such as rigidity or muscle contracture (dystonia)
• Difficulty with the physical production of speech or swallowing.
• Slow or abnormal eye movements.

Cognitive disorders

• Difficulty organizing, prioritizing or focusing on tasks
• Lack of flexibility or the tendency to get stuck on a thought, behavior or action (perseveration)
• Slowness in processing thoughts or ''finding'' words
• Difficulty in learning new information
• Lack of impulse control that can result in outbursts, acting without thinking and sexual promiscuity
• Lack of awareness of one's own behaviors and abilities

Psychiatric disorders​​​​​​​

• Feelings of irritability, sadness or apathy
• Social withdrawal
• Insomnia
• Fatigue and loss of energy
• Frequent thoughts of death, dying or suicide