Phenotypic Variability Flashcards
What is a common misconception when it come to genetic disease?
Everyone suffering the same genetic disease will have identical symptoms, disease course and prognosis.
Why may diseases with different causes be labelled by the same name?
Genetic disease are rare and classified by their symptoms
How is the classification problem being rectified?
Diseases are being reclassified with a sub-type
Give an example of a disease that has been sub-classified?
Osteogenesis Imperfecta
Other than genetics what other factor influences progress and outcome?
Environment i.e external factors
What is multiple endocrine neoplasia type 1? MEN1
Disease which increases chance of developing adenomas in endocrine tissue
Caused by mutation in tumour suppressor gene
Autosomal dominant
Why do people with MEN1 suffer from different types of tumour at different times?
Second event must occur to promote further tumour formation
Cause unknown
What is hereditary haemochromatosis?
Autosomal recessive gene
Mutation in homeostatic iron regulator protein
Leads to excess iron absorption
Why do only 10% of people with HFE clinically suffer?
Women- menstruation
Men- dietary load of iron varies and those with lower levels of dietary iron suffer less
Other than disease gene and environment, what other factor influences condition?
Presence of other genes
Give an example of where modifier genes influence disease phenotype?
Cystic Fibrosis
Patients with the same homozygous delF508 mutation can have severe or mild lung disease
What gene is associated with sever cystic fibrosis?
Gene encoding transforming growth factor Beta-1
What gene increase chance of developing which infection in cystic fibrosis sufferers?
Immunoglobulin Fc-gamma receptor II
Increases chance of developing chronic Pseudomonas aeruginosa infection
What is VHL?
Von Hippel-Lindau Syndrome
Dominantly inherited familial cancer syndrome
What does VHL cause?
Predisposition to malignant cancer and benign neoplasms
What alters the phenotype of VHL?
Cyclin D1
Increases number of retina, angiomoas
What are the two types of muscular dystrophy?
Duchenne and Becker
What causes muscular dystrophy?
Mutation in the dystrophin gene
What is caused by muscular dystrophy?
Muscle wasting and weakness
What is different about the Becker form?
Milder
Onset around 12 years can be much later
Death 40-50 yrs
What are the features of the Duchenne form?
Diagnosis at around 5years
Wheelchair dependency at 10 years
Death at median age of 17 years
Why are the two form of muscular dystrophy different?
Type of mutation
DMD- frame shift deletion
BMD- does not result in from shift
What are trinucleoside repeat disorders?
Trinucleotide repeat expansion
If fewer than 27 repeats- stable
The greater the number of repeats the more severe the phenotype
What causes Huntington’s disease?
Expansion of a region of CAG repeats in the Huntington gene
Results in the production of a polyglutamine tract
27 : stable
27-35: intermediate phenotype
36-39: characteristic phenotype not all carriers affected
40+: all carriers affected
