Its giving Mendel
BONUS: Is this GOF, LOF, or dominant negative?
Achondroplasia (GOF); exclusively paternal germline
Which disease: enlargement of posterior fossa snd elevation of tentorium; cystic dilation of 4th ventricle; partial/complete genesis of corpus callous; hydrocephalus present
DANDY WALKER
You decide to do shrooms. Sadly, you have picked the wrong type of shrooms to do. You took a huge concentration of shrooms, but your friend only took a low concentration of them. What is inihibited and what is the mushroom called?
A-amantin inhibits RP 2 at low concentrations, but inhibits RP 3 at high concentrations
Asymptomatic bony defect, tuft of hair, and skin intact are phenotypes of what disease? What went wrong in the womb?
Spina bifida occulta; fail of caudal closure of neural tube; vertebral arch defect
A patient comes to you and you see that they have a very small ear size. You talk to them and decide to do genetic testing. The results show mutations of genes involved in the preRC complex (ORC1, ORC4, ORC6, CDT1, CDT6). What disorder?
Meier-Gorlin syndrome
Which blood type is protected against plasmodium falciparum (malaria)?
BONUS: parasites bind to RBCs with preference for (order A, B, and O from most to least)
Type O; A>B>O
You run a prenatal genetic test and notice that the fetus has mutations in DCX or LIS1 gene. What disorder is present?
Lissencephaly, leading to smooth brain surface
What is an example of a mutation that affects RNA splicing that can be very detrimental to health? Name a clinical correlate.
BONUS: What gene is mutated?
Aberrant splicing, example is spinal muscular atrophy.
SMN1 is defected therefore there is not enough SMN protein to assemble snRPS which leads to neruomuscular degeneration
Mutations in the HBB gene cause reduced/absent B-globin production. What is this called?
B-thasssemeia
A patient has mutations in DNA recombination repair enzymes. You notice that they have premature aging and are immunodeficient. Which disease is this?
Ataxia-Telangiectasia
Mutations in DNA recombination repair enzymes that result in hypersensitivity to ionizing radiations; AT gene mutated leading to genomic instability; rare neurodegenerative disease; ataxia - poor coordination; telangiectasia - small dilated BVs; progressive cerebellar degeneration, telangiectasia, immunodeficiency, premature aging and predisposition to cancer development
Which disease causes an inversion of exons 1-22, seen in 1:500 live births, and can be treated with hemlibra? And is it X linked, autosomal, dominant, or recessive?
Hemophilia A; X-linked recessive
What is the difference between lobar, semi lobar, and lobar separations?
Lobar: no hemispheric separation, single ventricle, cyclopia
Semilobar: partial separation, cleft lip/palate
Lobar: near-normal separation; subtle midline defects
What disease is associated with mitochondrial aminoacyl-tRNA synthetase? What about cytoplasmic?
Mitochondrial: Leukoencephalopathy (brainstem and spinal cord causing slow progressive gait and ataxia OR with thalamus and brainstem with mild severe disease phenotype)
Cytoplasmic: antisenthetkase (autoimmune) and charchot marie tooth (motor and sensory neuropathy)
Which disease treatment uses exon skipping with ASO to reframe transcript and fix the reading frame?
Duchenne muscular dystrophy
Which rare autosomal recessive disease causes defects on proteins that participate in nucleotide esmzcision repair? Causes dry skin and lots of freckles?
Xeroderma pigmentosum
In Tay-Sachs Disease, what is mutated? What substance accumulates as a result? And what mode of inheritance is it?
Hexosaminadase A; accumulations of GM2 gangliosides (toxic to neurons); autosomal recessive
You see a patient who complains of a headache. For some reason, you decide to order a CT so that you can look at his brain. Well, it is a good thing you did, because now you see caudal descent of descent of cerebellar tonsils during foramen magnum. A large cerebellar tonsillar herniation is present. What is wrong with the patient?
Chiari malformation
Which disease is caused by aqueduct stenosis?
In sickle cell anemia, what is the amino acid mutation?
Transversion of GAG (glutamate) to GTG (valine); pts have increased resistance to malaria
In adenosine deaminase deficiency (ADA), there is damaged immune response leading to SCID. Pts are at higher risk for what type of infection? And why is there lymphotoxicity?
Opportunistic infections like pneumonia or chronic diarrhea. Lymphotoxicity due to increased dATP
For Fragile X, tell me: what it occurs through (oogenesis/spermatogenesis), what stage of mitosis fails, instance rates in males, what gene and protein is affected
BONUS: A mutation in that gene is also associated with what mental disability?
Triplet expansion occurs only through oogenesis; failure in chromatin condensation during mitosis; 1:3-4k live births, hypermethylation of CpG in 5'UTR of FMR1 gene. FMR1 encodes FMRP
FMR1 associated with autism
It's your first day as a GI doctor in your own practice. In your first solo colonoscopy, you see some polyps and decide to send them off to pathology. Pathology sends you results of a genetic screen and you see that there are mutations in mismatch repair enzymes, such as MLS1 and MSH2. These genes are nonfunctional, therefore they have lost the ability to remove single nucleotide mismatches. What cancer will you diagnose?
Hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome)
Explain what leads to defective CFTR channel processing, what mode of inheritance CF is, what levels are high in serum, and which class is the worst
Deletion of Phe inhibits dimerization, class V is the worse, AR with allelic heterogeneity, high levels of trypsin
Which disease occurs as a result of only 1 copy of functional telomerase RNA gene? Name 2 examples of symptoms
Dyskeratosis Congenital; progressive bone marrow failure, skin pigmentation, nail dystrophy, mucosal leukoplakia
IN Neurofibramotosis I, this is an autosomal dominant with ____ penetrance and _____ expression. Seen in 1/____ live births. What protein is affected?
100% penetrance and variable expressivity. Seen in 1/3500 live births. Mutation results in ras-GTP bound form so signaling continues and causes lots of cell proliferation which causes lisch nodules and tumors