biochem: genetics Flashcards
hypophosphatemic rickets
vit-D resistant. X-linked dominant. incr. phosphate wasting at proximal tubule
mitochondrial myopathies
rare, present w/myopathy, lactic acidosis, and CNS dz. caused by failure of oxidative phosphorylation. muscle Bx shows “ragged red fibers”
polycystic kidney dz
autosomal dominant. b/l massive enlargement of kidneys due to multiple large cysts. 85% due to PKD1 mutation on chromosome 16
familial adenomatous polyposis
autosomal dominant. colon becomes covered w/adenomatous polyps after puberty. progresses to CA unless colon is resected. mutations on chromosome 5q
familial hypercholesterolemia
autosomal dominant. defective/absent LDL receptor -> elevated LDL -> severe atherosclerosis, corneal arcus, tendon xanthomas
hereditary hemorrhagic telangiectasia
autosomal dominant. inherited disorder of blood vessels -> branching skin lesions, recurrent epistaxis, skin discolorations, AVMs, GI bleeding, hematuria
hereditary spherocytosis
autosomal dominant. spheroid erythrocytes due to spectrin or akyrin defect; hemolytic anemia; inc. MCHC, inc. RDW. Tx: splenectomy
HD
autosomal dominant. -> depression, progressive dementia, choreiform movements, and caudate atrophy. inc. DA, dec. GABA, dec. ACh in the brain. gene on chr. 4 - trinucleotide repeat d/o (CAG). demonstrates anticipation: more repeats -> younger age of onset
li-fraumeni syndrome
autosomal dominant. abnormalities in TP53 -> multiple malignancies at young age. sarcoma, breast, leukemia, adrenal gland.
marfan syndrome
autosomal dominant. FBN1 gene mutation on chromosome 15 -> defective fibrin (scaffold for elastin) -> connective tissue d/o. lens subluxation is typically upward
MEN
autosomal dominant. familial tumors of endocrine glands (pancreas, parathyroid, pituitary, thyroid, and adrenal medulla). MEN 1 - MEN1 gene. MEN 2 - RET gene
NF1
autosomal dominant. neurocutaneous d/o - cafe au lait spots, cutaneous neurofibromas, optic gliomas, pheochromocytomas, lisch nodules (pigmented iris hamartomas). 100% penetrance, variable expression. caused by NF1 mutation on chr. 17
NF2
autosomal dominant. b/l acoustic schwannomas, juvenile cataracts, meningiomas, and ependymomas. NF2 mutation on chr. 22 (NF2=chr22)
tuberous sclerosis
autosomal dominant. neurocutaneous d/o w/multi-organ involvement. numerous benign hamartomas. incomplete penetrance, variable expression
von hippel-lindau dz
autosomal dominant. development of many benign and malignant tumors. deletion of VHL tumor suppressor gene on chromosome 3p (3 word name)
autosomal recessive dzs
albinism, PKD, CF, glycogen storage dzs, hemochromatosis, kartageners, mucopolysaccharidoses (except hunter), phenylketonuria, SS anemia, sphingolipidoses (except fabry), thalassemias, wilson dz
CF mutations
typically CFTR on chr. 7. commonly Phe508.
CFTR encodes
ATP-gates Cl channels, secreting Cl in lungs and GI, reabsorbing Cl in sweat glands -> abnormally thick mucus
CF Dx
inc. [Cl] (>60mEq/L) in sweat. Can present with contraction alkalosis and hypokalemia (like loop diuretic). inc. immunoreactive trypsinogen on newborn screen.
CF complications
lung infections (pseudomonas), chronic bronchitis, bronchiectasis, reticulonodular pattern on CXR, pancreatic insufficiency, malabsorption w/steatorrhea and nasal polyps. meconium ileus in newborns. infertility in males. fat-soluble vit deficiencies (ADEK)
CF Tx
N-acetylcysteine to loosen mucus plugs (cleaves disulfide bonds w/in mucus glycoproteins), dornase alfa (DNAse) to clear leukocytic debris
X-linked recessive d/os mnemonic
Be Wise, Fool’s GOLD Heeds Silly HOpe: Bruton agammaglobulinemia, Wiskott-aldrich syndrome, Fabry dz, G6PD, Ocular albinism, Lesch-nyhan syndrome, Duchenne (and becker) muscular dystrophy, Hunter Syndrome, Hemophilia A and B, Ornithine transcarbamylase deficiency
Duchenne muscular dystrophy
Duchenne = deleted dystrophin. x-linked frameshift mutation -> truncated dystrophin -> inhibited muscle regeneration. Begins in pelvic girdle, progresses superiorly. Pseudohypertrophy of calf muscles due to fibrofatty replacement. Gower maneuver, waddling gait. Onset before 5. Die of dilated cardiomyopathy
Becker muscular dystrophy
x-linked non-frameshift insertions in dystrophin gene -> partially fxnal protein -> less severe, later onset.
myotonic type 1 muscular dystrophy
autosomal dominant. CTG trinucleotide repeat expansion in DMPK gene -> abnormal expression of myotonin protein kinase -> myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia. My Tonia, My Testicles, My Toupee, My Ticker
Fragile X syndrome
x-linked defect affecting methylation and expression of FMR1 gene = 2nd most common cause of genetic intellectual disability. Post-pubertal macroorchidism, long face w/large jaw, large everted ears, autism, miral valve prolapse
trinucleotide repeat expansion dzs mnemonic
Try hunting for my fried eggs: Huntington’s, myotonic dystrophy, friedreich ataxia, fragile X. or X-Girlfriend’s First Aid Helped Ace My Test.
chr. 3 d/o
von hippel-lindau, renal cell carcinoma
chr. 4 d/o
ADPKD w/PKD2 defect, HD
chr. 5 d/o
cri-du-chat syndrome, familial adenomatous polyposis
chr. 7 d/o
williams syndrome, CF
chr. 9 d/o
friedreich ataxia
chr. 11 d/o
wilms tumor
chr. 13 d/o
patau syndrome, wilson dz
chr. 15 d/o
parader-willi, angelman syndrome
chr. 16 d/o
ADPKD w/PKD1 defect
chr. 17 d/o
NF1
chr. 18 d/o
edwards syndrome
chr. 21 d/o
down syndrome
chr. 22
NS2, digeorge syndrome (22q11)
chr. X d/o
fragile X, X-linked agammaglobinemia, klinefelter
robertsonian translocation
long arms of 2 acrocentric chromosomes fuse at the centromere and 2 short arms are lost. balanced translocations -> normal phenotype. unbalanced translocations -> miscarriage, stillbirth, chromosomal imbalance
cri-du-chat syndrome
congenital microdeletion of 5p -> microcephaly, intellectual disability, high-pitched crying, epicanthal folds, VSD
williams syndrome
congenital microdeletion of 7q (including elastin). -> elfin facies, intellectual disability, hypercalcemia (inc. vit. D sensitivity), good verbal skills, extreme friendliness, CV problems
CATCH-22 syndrome
microdeletion of 22q11 -> variable: cleft palate, abnormal facies, thymic aplasia (-> T cell deficiency), hypocalcemia (2/2 parathyroid aplasia). digeorge: thymic, parathyroid, and cardiac. velocardiofacial: palate, facial, and cardiac
