Diseases Flashcards
What are the clinical features of Fragile X Syndrome?
long face
big ears
hyperextensible joints
moderate/ severe mental retardation in males
learning disabilities/ mild retardation in females
What is the inheritance pattern of Fragile X Syndrome?
X linked dominant with Sherman Paradox
What is a key feature of Fragile X Syndrome pedigrees?
Males never have affected daughters and the reason for that is unknown.
Premutation females have what number of CGG repeats in Fragile X Syndrome?
50-100 CGG repeats
They have a normal phenotype but have a high risk of having affected offspring.
70 CGG = 50% of offspring will have full mutation
> 90 CGG = always pass on full mutation to offspring
What is the genetic basis of Fragile X Syndrome?
It is when you have 800-1000 CGG repeats. This is a huge expansion that prevents transcription due to CpG hypermethylation in 5’ UTR. It expresses no FMR-1 mRNA. There is a loss of function.
What is the Sherman Paradox?
It is when there is an increasing risk of full expansion (affected children) depending on the size of their allele.
What is the inheritance pattern of Myotonic Dystrophy?
Autosomal dominant with anticipation
What is anticipation?
Anticipation is when there are more severe symptoms and earlier onset in successive generations. There is a successive generational expansion of CTG triplet.
What are the clinical features of Myotonic Dystrophy?
Normal intelligence
Mild Cases: cataracts, prefrontal baldness, no mytotonia
Adult Onset: muscular dystrophy and cardiac arrhythmia
Severe Cases: congenital onset and rapid progression of muscle degradation
What is the genetic basis of myotonic dystrophy?
There is a CTG expansion in the 3’ UTR of the DM-1 gene.
400: adult onset
>1000: congenital
T/F: DM-1 protein is not made in normal amounts in the affected patients of Myotonic Dystrophy.
False. DM-1 is made in normal amounts but the defect is caused by gain of function in DM-1 mRNA (i.e. toxicity).
What is locus heterogeneity?
Is is when mutations on different genes cause the same disease. For example, CCTG mutations on a second locus ZnF9 causes DM-2, which has the same phenotype as DM1 which is caused by mutations on DMPK gene.
What is the inheritance pattern of Huntington’s Disease?
Autosomal Dominant with anticipation
What are the clinical symptoms of Huntington’s Disease?
Progressive chorea (jerky movements)
Rigidity
Dementia
Death 10-15 years after onset
Age of onset correlate with ______ in Huntington’s Disease.
the number of CAG triplet repeats in the protein coding region of the gene.
Why is there variability in the age of onset in HD?
It is caused by anticipation! A small increase in the number of CAG repeates causes a decrease in the age of onset
T/F: HD is caused by a gain of function toxic protein that has larger poly-glutamine tract.
True.
What is another name for Kennedy disease?
Adult onset spinal bulbar muscular atrophy
T/F: The androgen receptor gene is X-linked.
True.
What is the genetic basis for Kennedy disease?
It is caused by expansion of the CAG triplet in the coding region of AR gene causes GAIN OF FUNCTION in the androgen receptor.
What causes complete testicular feminization?
It is caused by androgen receptor LOSS OF FUNCTION causing XY females.
What is the inheritance pattern of multifactorial diseases?
Autosomal dominant (predisposition)
What is thrombophilia?
It is the propensity to form blood clots within blood vessels: deep vein thrombosis
What is the primary cause of pulmonary embolisms?
DVTs
What causes Factor V Leiden Disease?
G to A mutation causes ARG –> GLN substitution in proteins.
Protein C does not inactivate Factors 5,8
What causes Long QT syndrome?
It is caused by mutations in potassium channels which cause the slow repolarization of membrane causing a long QT interval
What does Long QT mutations give you predisposition to?
Arrythmia and sudden death
What is the treatment for Long QT?
pacemakers and drug therapy
Why don’t 100 percent of twins both have hypertrophic cardiomyopathy?
Genetics is just a predisposition, not a guarantee for the disease.
What is hypertrophic cardiomyopathy?
It is the thickening of the walls of the heart.
What are two of the most common genes that predispose you to HCM?
MYBPC3 and MYH7
What is the most common cause of sudden death in young adults?
HCM (hypertrophic cardiomyopathy)
What are some treatments that are available for HCM patients?
genotyping array
implanted defibrillators
test family members/ young athletes
T/F: Mutations in cardiac contractile protein genes are known to increase risk for HCM.
True.
What is Alzheimer’s disease?
It is a central nervous system neurodegenerative disorder with a progressive loss of cognitive function and dementia.
What causes death in patients with Alzheimer’s disease?
Death from malnutrition, infection and heart disease
What percentage of people have early onset autosomal dominant Alzheimer’s Disease?
5%
What genotype is high risk for late onset Alzheimer’s?
E4E4
Mutations in which three genes can predispose you to early onset Alzheimer’s?
APP
presenilin1
presenilin2
Common variants in _______ predispose you to classic Alzheimer’s disease.
apolipoprotein E
Accumulation of which aberrantly processed polypeptide causes Alzheimer’s?
beta amyloid polypeptide
