Genetics Lecture 2, Exam 2
Terms in this set (89)
Neurodegenerative disorder that accounts for about 60-80% of dementia cases. What are the two versions?
Late onset LOAD- more common
Early onset EOAD
AD IS NOT ASSOCIATED WITH
Al cans or pots
Non modifiable risk factors for AD:
2. Family Hx
3. Numerous Genes including certain ______ alleles
= 3-15X more risk for ______
APOE _____ = relatively rare and may confer some protection
APOE ____ = most common allele, neutral effect
APOE _______ =
present in 10 to 15% percent of the population and in about 40% of people with late-onset Alzheimer's
Which APOE combination has the highest risk for development of AD? Second highest risk?
The following are
modifiable risk factors
___ damage risk - (diabetes, high cholesterol and HTN)
Low educational level
Prior head injury
____ replacement therapy
This is also called Familial AD (FAD) and accounts for less than 5% of Alzheimer's cases and is associated with a family history
Age of onset for EOAD?
mutations in these genes are associated with __________
Characterized by amyloid plaques and/or neurofibrillary tangles?
Treatment of Mild to Moderate AD?
Acetylcholinesterase inhibitors like Razadyne, Exelon, Aricept
______ are used to treat the cognitive symptoms (memory loss, confusion, thinking issues) associated with AD.
These compounds may also help in patients with mild cognitive impairment who do not have AD
_____ is used to treat
moderate to severe AD
It is a ______that delays the progression of some symptoms.
NMDA receptor antagonist
This is a combination of memantine (Namenda) and donepezil (Aricept) that is used to treat moderate to severe AD?
, genetic testing is used ONLY for people with a family history of _____.
Genetic testing is NOT generally recommended for people at risk of _____
, genetic test to identify ______ alleles BUT there is NO specific or preventive treatments available
Western European ancestry
Affects men and women equally; imprinting affects presentation
mutations in the
that results in a
People with 27-35 repeats don't develop _____ but are at risk of having children who will develop the disorder
Symptoms of HD usually emerge in 30s- 40s but can be onset before 20 with ___
Negative Test result for HD= _____ CAG repeats
Positive= more than ______ repeats
36-39 would be uninformative
With HD the increase in CAG segment leads to the production of an abnormally long ________ that cuts into smaller fragments that aggregate.
Accumulated fragments are neurotoxic
Muscle problems, such as rigidity or dystonia
Slow or abnormal eye movements
Impaired gait, posture, and balance
Difficulty with the physical production of speech or swallowing
Deterioration of cognitive function
Emotional/ mental disturbances
Sx of HD
Median survival time for HD is ____ years after symptom onset
How do we confirm presence of HD?
Management of HD-associated chorea?
2. atypical neuroleptics-olanzapine
4. monoamine depleting agent tetrabenazine
Management of myoclonic hyperkinesia associated with HD?
Management of hypokinesia and rigidity associated with HD?
This is associated with a progressive neurodegeneration within the substantia nigra with risk increasing with age
are __________ genes affected by PD
are ________ genes affected PD
Most Parkinson's is managed with _______
Most common fatal
genetic disorder in children?
Average life span of CF patients? Most common cause of death?
respiratory failure (liver 2nd)
Is CF a part of newborn screening?
Mutated CFTR gene?
Most common mutation in all ethnic groups is a 3 base pair deletion (ΔF508 CFTR)
Typical clinical manifestations of cystic fibrosis usually do not occur in patients who have (_)% or more CFTR function
Initial NBS looks for ______ in CF patients?
immunoreactive trypsinogen (IRT)
this catches 90-95% children who don't have a meconium ileus at birth
66% diagnosed within 1st year of life. If not detected by NBS, usually detected by age 3 to 4 yrs
CF Phenotype depends on the CFTR allele, environment, and _______. CF has a multi system impact.
95% of males with CF have ______
CBAVD aka Congenital bilateral absence of Vas Deferens
Normal CFTR has different roles in different types of epithelial cells:
-____ and fluid secretion in airways and submucosal glands
-Reabsorption of ______ from sweat
Mutated CFTR leads to high levels of _____ in sweat hyperabsorption of _______.
Reduced _______ secretion leads to decreased airway surface liquid. Mucus layer of lung adheres to cell surface disrupting cough and cilia dependent clearance
Recurrent bacterial infections in the LRT?
increased salt loss in sweat
90% of patients
Limited secretion of lipase, trypsin, chymotrypsin leading to poor growth/poor weight gain despite normal food intake?
Pancreatic Insufficiency with CF
Accumulation of these 3 enzymes lead to pancreatic fibrosis and cysts and _______
cystic fibrosis-related diabetes (13%)
Treatment Goals for CF:
1. prevent/manage lung infections with ____
2. loosen/remove mucus from lungs
3. prevent and treat _______ blockage
4. provide adequate ____ with pancreatic enzyme supplements
This will prolong the survival of CF patients (1 year >80%, 5-year 60%)
Approaches to Gene Therapy:
1. replace a mutated gene that causes disease with a _____ copy
2. ____ or knock out, a mutated gene
3. ____ a new gene to help body fight
Gene Therapy for CF:
1. Latest phase 2 - inhaled DNA in ________
2. Past studies- adenoviral vectors to deliver functional CFTR and liposome transfer
Most clinical trials in gene therapy have been aimed at treating _____ via:
inserting tumor suppressor genes, immunotherapy, oncolytic virotherapy, and gene directed enzyme pro-drug therapy
Vectors for gene therapy
Naked plasmid DNA
1. larger _____ capacity
2. high efficiency in _____
3. high levels of _____
4. infect _______ cells
1. ____ concern
2. less DNA ___ capacity
4. innate inflammatory response against capsid protein
Chronic disease of the heart muscle that can be either acquired or inherited?
This is the
most common type
of cardiomyopathy that affects more men than women ages 20-60.
Often starts in the _____ then spreads to right ventricle and atria. Heart weakens and fails.
This cardiomyopathy is a
less common type
in which the rigid ventricles restrict diastolic period. It mostly affects ________ adults
Connective tissue disorders.
Some cancer treatments, such as radiation and chemotherapy.
The above are all potential etiologies of _______
Characterized by unexplained left ventricle hypertrophy (LVH) and occurs in absence of abnormal-loading conditions like arterial hypertension or valve disease
HCM has an _______ inheritance pattern
Most common monogenic cardiovascular disorder in US and leading cause of sudden cardiac arrest in young people/athletes
Mostly affects high school athletes
This type of cardiomyopathy EQUALLY effects men and women?
Autosomal dominant inheritance involving the following genes:
The defective genes that cause _______ encode sarcomere proteins
-Noninvasive cardiac imaging such as echocardiography or cardiac MRI shows wall thickness _____ in one or more LV segments
-Autopsy ____ : myocyte disarray & fibrosis
< 15 mm
Physical Findings in HCM:
Double Apical Impulse
Prominent LV pulse/Apical Lift
Brisk Carotid Upstroke
EKG-tall R wave, inverse T wave, wide QRS
Invasive septal reduction
Pacemaker of ICD
are all treatment options for ______
In HCM, we want to avoid
vigorous activity, ________ and medications that decrease ______ such as ACEI, ARBs, and other direct vasodilators
Most cases of _______ are due to HCM; but there are other causes:
Inborn errors of metabolism
This is a situation in which
myocytes of right ventricle die
and are replaced with fatty/fibrous tissue.
Most commonly the right ventricle apex and outflow tract are involved
Arrhythmogenic Right Ventricular CM (dysplasia) (ARVC/D)
ARVC/D has what type of inheritance with what type of mutation?
autosomal dominant with desmosomal protein mutation
_______ disrupts the heart's electrical signals and causes arrhythmias. It usually 1st manifests in teens or young adults and can be
(not THE) of the leading cause of cardiac arrest in athletes.?
______ should be suspected if :
Chest pain ± rise in cardiac biomarkers
Dilated cardiomyopathy with early onset and frequent ventricular arrhythmias
Precordial T-wave inversions beyond V1
Sporadic ventricular ectopic beats, subtle ECG/morphologic abnormalities, possible sudden death (sports restriction mandatory)
Severe arrhythmia symptoms or sustained ventricular tachycardia (VT), diffuse RV/LV structural abnormalities, possible sudden death
Overt Electrical Heart Disorder ARVC
Increased dilatation, decreased contractility of RV/LV, heart failure symptoms, sustained VT
Biventricular Pump Failure ARVC
Therapies for _____ are aimed at
preventing heart failure, malignant arrhythmias, and sudden cardiac death
Class III antiarrhythmic (sotalol, amiodarone) therapy if there are unacceptable # of ICD discharges for patients with ARVC/D
NO SINGLE DIAGNOSTIC TEST DEFINITIVE FOR ______
Wide Split S2,S3, S4
Asymmetry of Chest Wall (RVD)
T wave inversion
Prolonged S wave
-little waves of grass on hill
This is the most SPECIFIC finding of ARVC? seen in 30% patients?
Epsilon Wave on ECG
Diagnosis of ______ requires:
2 major criteria
1 major and 2 minor criteria
4 minor criteria of different categories
Major criteria for ARVC:
1. RV Dysfunction
2. Myocardial tissue characterization - fibro/fatty
3. _____ or ____ Abnormalities
5. Family History
Clinical manifestations of BOTH _____ and ______:
From asymptomatic to progressive heart failure to SCD
Orthostasis, pre-syncope; syncope