Chromosomes/Genetics Flashcards
Retinoblastoma
13
Osteogenesis Imperfecta
AD
Decreased production of type 1 collagen. Brittle bone dz, blue sclerae
Prader-Willi
Paternal deletion on cs 15, maternal imprinting (maternal gene silenced via methylation)
Angelman
Maternal gene is deleted/mutated on cs 15, paternal imprinting
Lesch-Nyhan Syndrome
XLR
Defective purine salvage due to absent HGPRT (converts hypoxanthine to IMP and guanine to GMP ==> excess uric acid prod and de novo purine synth
Orotic Aciduria
AR
defect in UMP synthase, converts orotic acid to UMP
Get orotic acid in urine, megaloblastic anemia that doesn’t improve with folate or B12, FTT
OTC deficiency: get hyperammonemia AND orotic acid in urine/blood
I-cell disease
inherited LSD, defect in phosphotransferase ==> failure of golgi to phosphorylate mannose residues on glycoproteins, protons secreted extracellularly rather than delivered to lysosomes
Coarse facial fx, clouded corneas, restricted joint mvmt, high plasma lysosomal enzymes, often fatal in childhood
Huntington Disease
AD, cs 4, CAG repeat
decreased levels of GABA and ACh
neuronal death via NMDA-R binding and glutamate toxicity. Atrophy of caudate nuclei on imaging
CS 7 mutations:
CF, Ehlers-Danlos syndrome, osteogenesis imperfecta
CS 16 mutations:
PCKD, tuberous sclerosis
CS 20 mutation:
MODY
Friedreich Ataxia
AR, cs 9, GAA repeat, degen of cerebellum and spinal cord tracts
Encodes frataxin: mitochondrial iron regulation, buildup of iron –> free radical damage
Presents in childhood w/ kyphoscoliosis
mm weakness, loss of DTRs, vibration, propriocep. Staggering gait, falling, nystamus, dysarthria, hammer toes, pes cavus, HCOM
ras
proto-oncogene,
bladder, lung, colon, pancreas, kidney cancer
N-myc
proto-oncogene
neuroblastoma, small cell lung carcinoma
BRCA-1 and 2
Tumor suppressors, DNA repair genes
breast and ovarian cancer
NF-1
tumor suppressor, cs17
neuroblastoma, NF-1, sarcomas
ERB-B1
Proto-oncogene
Squamous cell lung carcinoma
APC/beta-catenin
Tumor suppressor
gastric, colon, pancreatic cancer, FAP
ERB-B2
Proto-oncogene
breast and ovarian cancer
DCC
Tumor suppressor
Colon cancer
TGF-alpha
Proto-oncogene
astrocytoma, hepatocellular carcinoma
p53
Tumor suppressor, inhibits prolif of cells with genetic abnormalities
Most cancers, Li-Fraumeni syndrome
sis
proto-oncogene
astrocytoma, osteosarcoma
RB
tumor suppressor, suppresses the transition from G1 to S phase, inhibits proliferation
retinoblastoma, osteosarcoma, others
abl
proto-oncogene
CML, ALL
WT-1
tumor suppressor
Wilms tumor
NF-1
cs 17
Cafe au lait, lisch nodules, neurofibromas, inguinal/axillary freckles, optic nerve gliomas, pseudoarthrosis and other bony abnormal
Assoc tumors: meningiomas, astrocytomas, gliomas, pheochromocytomas
ADPKD
Bilateral, assoc w/ polycystic liver dz, berry aneurysms, MVP
PKD1: cs14 (85%)
PKD2: cs4
FAP
presents after puberty, AD, cs5
NF type 1:
cs17, AD, 100% penetrance
NF type 2:
cs22, AD
Bilat acoustic schwannomas, juvenile cataracts, meningiomas, ependymomas
VHL
cs3, tumor suppressor gene
multiple bilat RCC, hemangioblastomas of retina/cerebellum/medulla
CF
AR, CFTR gene on cs7
MC lethal genetic dz in caucasian pop
CFTR encodes ATP gated Cl- channel
Mutated protein retained in RER
More negative transepithelial potential difference b/c increased Na+ reabsorp
Myotonic type 1 muscular dystrophy
CTG trinucleotide repeat expansion in DMPK gene
Abnormal expres of myotonin protein kinase –> myotonia, muscle wasting, frontal balding, cataracts, testicular atrophy, arrhythmia
Slow relaxation: “difficulty releasing doorknob”
Biopsy: type 1 muscle fibers have more atrophy
Downs quad screen (second trimester):
Increased: hCG, inhibin A
Decreased: AFP, estriol
First trimester US: nuchal transluc, hypoplastic nasal bone
PAPP-A is decreased
Edwards quad screen:
Everything decreased! (AFP, hCG, estriol, inhibin A)
micrognathia, low set ears, clenched hands
Patau first trimester pregnancy screen:
decreased: free hCG, PAPP-A
Nuchal translucency
cleft lip/palate, holoprosencephaly, polydactyly
Cri du chat:
cs 5 short arm microdeletion
microcephaly, intellec disabil, high pitched cry/mew, epicanthal folds, cardiac abnorm (VSD)
Williams syndrome
cs7 long arm microdeletion - deleted region includes elastin gene
elfin facies, intellectual disability, hypercalcemia (increased vit D sensitivity), well devel verbal skills, extreme friendliness with strangers, CV problems