Genetics Flashcards
How do you manage Wilson’s?
Penicillamine ro chelate the copper
Gene and Chromosome in Wilson’s disease
ATP7B, chromosome 13
What explains connection of Down’s syndrome and Alzheimer’s?
Presence of APP gene on chromosome 21. There’s cleavage of APP from A beta amyloid. Whc8h accumulates in brain tissue and vessel walls. There are three copies of APP gene.
Central hypoginadismo, amosmia y delayed puberty Dx?
Kalilman Syndrome.
Gene mutated in Kali an syndrome
Gene KAl-1 or the fibroblast grown factor receptor -1 gene.
Duchene has dystrophin gene protein (absence or reduced)?
Absent
Genotype in Klinefelter syndrome
47 XXy is most common
Characteristic in kilnefelter
Mental disability or normal, testicular failure y def in testosterone because of fibrosis and hyalinization of seminiferous tubules., euchonoid body habitus, tall, gynecomastia, because of def of testosterone.
Gene in galactosemia and sx
GALT, galactose 1 phosphate uridylyransferase — complete absence of this enzyme leads to jaundice, vomiting, hepatomegaly, failure to thrive, poor feeding, lethargy, diarrhea, sepsis.
In galactosemia, sepsis can occur as a result of what organism?
E. coli
Cardiovascular finding in turner syndrome
Coarctation of aorta pre ductal, also bicuspid aortic valve, aortic dissection in adults. Almost 30% of children with it have pre ductal.
Sx of pre ductal aortic coartctation in children with turners syndrome
Diminished femoral pulses compared to brachial pulses.
How do you Dx Hereditary osherocytosis?
Osmotic fragility test
How do you Dx paroxysmal nocturnal hemogkobinuria?
Hams test
How do you Dx autoimmune hemolytic anemia?
Coomb’s test
Late onset Alzheimer’s is associated with the presence of the —— allele of the ———- protein. This protein is involved in forming senile plaques. Early onset of Alzheimer’s is associated with the presence of te ——- protein on chromosome 21.
Allele e4, ApoE4, amyloid precursor protein
Twins with disease expressed in varying degree of severity, I’d due to what?
Variable expression
Mixture of two types of materials leading to clinical variability
Heteroplasmy
Phenotype dependent on whether mutation comes from mom or dad
Imprinting
Mutation of a tumor suppressor gene occurs and complementary alleles must be deleted or mutated before cancer delevelios
Loss of heterozygocity
Not all of those with the affected genotype will show it phenotypically
Incomplete penetrance
Prominent occiput, micrognathia, low set ears or malformed, small mouth. Rocker bottom feet, overriding fingers
Edwards Syndrome, trisomy 18
Imprinting of paternal chromosome 15, hyperphagia, obesity, delayed puberty, GH deficiency
Prader willi
Down’s syndrome patients have a high as much as 20 fold increased chance of developing ——- leukemia early on, as well as ——- leukemia in their lifetime.
ALL, AML
A single genetic defect affects more than one organ system
Pleiotrophy
Chromosome affected in Fragile X?
What is the tricucleaotide repeat?
What does this repeat cause?
x chromosome, CGG
Hypermetylation of cytosine bases, leading to gene inactivation subsequently
In CF, how do you loosen the mucus?
N acethylcysteine
What is the MEchanism of N acetylcysteine?
Cleaves the disulfide bonds within mucous glycoproteins
Severe degeneration of retina ganglion cells and their axons, near complete loss of central vision in one eye,
Lever hereditary optic neuropathy
Mode of inheritance of lever hereditary opctic neuropathy
Mitochondrial disease
Cause of testicular failure in klinefelter disease
Hyalinization and fibrosis of the seminiferous tubules and then lack of testosterone synthesis . Testicles are thus firm and small, and azoospermia happens. Infertility and absence of secondary characteristics.
29 year old with elbow and knee pain, came out of nowhere that pain, and also dark skin on the right ear. Brother and aunt with similar findings
Alkaltonuria , joint pain, dark spots on ears, sclera, nose,
Gene mutated in Alkaptonuria
HGD Homogentisic acid oxidase enzyme,
What is te problem in alkaptonuria?
Body cannot break tyrosine and phenylalanine so homogentisis acid oxidase builds up in skin and joints. And tissues.
Also known as hyperimmunoglobulin E syndrome
Job syndrome
Abnormal neutrophil chemotaxis, and mutation in STAT3 gene
Job syndrome
Job syndrome is a mutation in what gene?
STAT3 gene
A boy with coarse fáciles, absseses due to Staph aureus, Primary teeth retained, IgE elevation in blood and eczema
Job syndrome
A person with genetic predisposition to earlycancer development caused by a mutation in p53 gene
Li fraumeni Syndrome
What is the normal function of gene p53?
Prevents damage to cells by arresting mutant DNA in the G1/S stage of te cell cycle until damage is repaired.
Rapid development of malignant tumor at a young age (less than 45 years old), family history of cancers.
Li fraumeni Syndrome, p53 gene mutation
Genetically, What must happen before a person experiences a malignant tumor in li fraumeni Syndrome?
They must inherit 1 mutant allele of the p53 gene, then experience a somatic mutation of the second good allele.
A person with acute abdominal pain, peripheral neuropathy, and CNS signs. No rash
Acute intermittent porphyria
Enzyme deficient in acute intermittent porphyria?
Porphobilonogen deaminase
A person with pain in the abdomen, anxiety, hallucinations, agitation or delirium, patchy neuropathies, dysuria, retention of urine or incontinente, darkening of urine, was taking barbiturates or OCPs or Sulfas
Acute intermittent porphyria
Deficiency in enzyme in ferrochelatase
Protoporphyria
Deficiency in uroporphyrinogen III decarboxylase
Porphyria cutánea tarda
Mutation in the VHL gene disrupting the ubiquitin ligase complex
Von hippel lindau
A mutation in gene VHL causes an accumulation of ————, a hypoxia producing factor expressed during hypoxia conditions.
HIF-1 alpha
HIF-1 alpha is normally expressed under hypoxia conditions to produce a variety of proteins such as ——,——-,——-, and ——-.
PDFG, VEGF, EPO, TGH-alpha which create more blood vessels so more blood can come in so more oxygen can arrive.
In Von hippel lindau, there is an over expression of a factor whose role is to increase blood vessels and oxygen .
Hypoxia inducing factor 1 alpha
Two malignancies related to VHL mutation
Hemangioblastoma and renal cell carcinoma . These are sufficient for a Dx of von hippel lindau
vWF is a cofactors of factor ——.
Factor 8. Von willenbrand factor is a protector of factor 8
VW disease has three types: types —- and —- are autosomal dominant and type —— is autosomal recessive.
Types 1 and 2, type 3
Von willenbrand disease is caused by a deficiency in ——- in the ——-gene located in chromosome —-.
VWF deficiency, gene vWF, chromosome 12
VWF is required for ———-
Platelet adhesion.
VWF aids clotting by binding to: ——, ———-,——— and ——-,
Exposed collagen, gp1b, platelets, factor 8.
Deficiency in gp1b
Bernard soulié
Deficiency in gp2b3a
Glanzman thrombastemia
The drug ——- prevents platelet adhesion by inhibiting gp1b
Clopidogrel
The drug ———,———- and ———prevent pkatelet aggregation by inhibiting gp2b3a
Abxicimab, agrostat, integrilin
A presentation of easy bruising, nosebleeds, heavy menstrual periods, blood loss in childbirth
VW disease
Type one Von willenbrand disease is due to what?
Quantitative problem
Type 2a of vWDisease is due to what?
Qualitative defect in vWF, normal quantity, doesn’t bind collagen very well
Type 2b of vWDisease is due to what?
Hyperbonding of vWF to gp1b leading to reduction in available vWF as well as decreased platelets
Type 3 vWDisease is due to what?
Complete absence of vWF, most severe form
Newborn, cleft palate, rounded soles on bottom of feet
Patau, chr. 13
21 year old, reddish rash on face since childhood, lighter patches of skin on her arms
Tuberous sclerosis
Blood in urine, flank pain, 29 year old, elevated bp on multiple occasions
ADPKD
Gene affected in duchenne muscular dystrophy
Xp21 Febe, dystrophin Febe, dystrophin protein, can’t walk by 12. Dx before 6, growers maneuver, muscle replaced by fat
Inheritance of duchenne muscular dystrophy
X linked recessive
Kyphosis and lordosis are common back problems later in life in this disease
Achondroplasia, inherited autosomal dominant
Achondroplasia is due to mutation whereby a ——— is replaced by a ——- and there’s an kverexpression of ——+
Glycine, arginine, FGFR3
Glycine is replaced by arginine, lverxpressionnof FGFR3
Achondroplasia
How do you Dx vWDisease?
Measure vWF quantity in antigen assay. Measure its function via: gp1b binding assay Collagen binding assay Ristocetin cofacfor assay
How do you manage vWDisease?
Give desmopressing to release vWF from weibel palace bodies in endothelium
What is Ristocetin and How does risticetin work for vWDisease Dx?
It is a formerly used antibiotic. Let do thrombocytopenia and platelet agglutination. You give it and if there is clotting then that means that there is vWF present.
How is desmopressing administered in vWDisease?
Nasally
Essential tremor worsens with ——- and ——-. And it is most commonly seen in what part of the body?
Worsens with eating and holding an object.
Seen in upper extremities.
——-improved essential tremor
Alcohol does improve essential tremor.
How do you manage essential tremor?
Propranolol. — a non selective beta blocker
Physiologically, What causes essential tremor? Triggered by what?
Caused by elevated levels of epinephrine . Caffeine can be a trigger.
