Vignettes

Question 1

Cystic Fibrosis:

• Common symptoms? (2)
• CF gene codes for?
• Inheritance pattern?
• Where is CF gene located? How big? How many mutations ID-ed? Most common?
• Pathophysiology: Sinuses? (2) Lungs? (2) Pancreas? (2) Intestine? Liver? Vas Deferens? Sweat glands?

Answer 1

• Sinopulmonary infections; malabsorption nutritional abnormalities
• CFTR protein Cl ion channel
• AD
• Chrom 7; 250,000 BP’s, 27 exons; 1k; F508
• sinusitus, polyps; bronchiocephatis, endobronchitis; exocrine insufficiency, diabetes; meconium ileus; focal sclerosis; fail to develop; salt losing dehydration

Question 2

Cystic Fibrosis:

• Beonchioctasis? Leads to?
• Ways to diagnose CF? (4)
• Standard therapeutic therapy? (5)
• Therapeutics for abnormal genes? Abnormal CFTR? Altered transport? Infection? Destruction?
• CFTR protein: Type of protein? Structure? How many nu- binding domains? Highly charged what?

Answer 2

• Localized, irreversible dilation of bronchial tree; obstructive lung disease
• NBS with 2 CF mutations; >1 clinical feature of CF; family history; sweat chloride >60 mmol
• Pancreatic enzyme, inhaled AB, mucolytic agent; salt; vitamins
• gene therapy; protein rescue; fix ion transport; anti inflammatory; transplant
• ABC (ATP binding cassette) protein; 2, 6 membrane spanning domains; 2; regulartory (R) domain

Question 3

Lung cancer:

• What do prognostic markers tell us? With therapeutic intervention? What information for individual?
• What do predictive biomarkers tell us? Therapeutic intervention? What information for individual?
• Therapies if EFGR/HER is overexpressed? (2) Name of drugs?
• High EFGR expression in stage 3/4 with late stage NSCLC? Works better in who?
• EML4-ALK fusion treated how? Tests for this? (4) Only approved thus far?
• 2 diagnostic tools? Benefits/ disadvantage?

Answer 3

• Survival based on natural course of the disease; no; risk of relapse
• Outcome based on a specific therapy; yes; who will benefit
• TKI with mutated EGFR = Gefitinib
  Monoclonal AB = Cetuximab
• FLEX; caucasians
• ALK therapy; FISH, DNA sequencing, immunohistochemistry; RT-PCR reverse transcr.; FISH
• Chest X Ray
• Low dose fast spiral CT; picks up more, earlier but 95% false positives; need biomarkers

Question 4

Hypertrophic CM:

• Hypertrophy of? Due to?
• Inheritance? Penetrance?
• Prevalence?
• Secondary causes? (4)
• Majority of mutations?
• Cardiac myocyte hypertrophy? Myocyte disarray? Interstitial fibrosis? Dysplastic arterioles?
• Majority with the disease? Some? Few?
• What do they present with? (3)

Answer 4

• Myocytes; point mutation in sarcomere proteins
• AD; incomplete
• 1:500
• Hypertension, obesity, CHD, aortic valve disease
• missense
• organ hypertrophy, compromised function, arrythmia, ischemia
• Assymptomatic, dyspnea, angina, syncope; sudden death
• murmur, pump failure, arrythmia

Question 5

Malignant Hyperthermia:

• 70% mutation to what? Inheritance?
• Environement trigger? Ex? (2)
• Progression? (3)
• Treatment?
• What is myostatin? Mature muscle cell division? What happens instead? Mutation to myostatin? Heterozygous? Homozygous?

Answer 5

• RyR protein; AD
• Anesthesia; Inahalation of Halothane and Succinylcholine
• Increased intracellular Calcium; sustained contraction (part. masseter); hyperthermia
• Dantrolene
• Muscle growth regulator; doesn’t happen; increased length and girth; increased muscle size; bigger; yoked

Question 6

Duschenne MD:

• Inheritance?
• Test for it?
• Mutation to?
• How do they typically die?
• DMD mutation type? Beckers?
• Treatment? (2)

Answer 6

• X linked
• Gowers
• Dystrophin
• Cardiopulmonary; cardiomyopathy
• Big deletions/frameshift; in frame deletions
• surgical tendon release; corticosteroids