Term
| what are the three types of mendelian disorders |
|
Definition
autosomal dominant
autosomal recessive
sex-linked disorders |
|
|
Term
| what are the 4 autosomal dominant disorders |
|
Definition
| marfans, loeys dietz, ehler's danlos, familial hypercholesteroemia |
|
|
Term
| what are the 5 autosomal recessive disorders |
|
Definition
| PKU, galactosemia, lysosomal storage diseases, glycogen storge diseases, alkaptonuria |
|
|
Term
| what are the 4 lysosomal storage diseases and their subdiseases |
|
Definition
G2 gangliosidoses - tay sacs
neiman pick - A, B, C
gaucher's disease - 1-3
mucopolysaccridoses - hurler, hunter |
|
|
Term
| what are the 2 glycogen storage disease |
|
Definition
|
|
Term
| what are two ways to get an autosomal dominant disorder |
|
Definition
spontaneous mutation (usually in gametogenesis)
at least one affected parent |
|
|
Term
| why might someone get an autosomal dominant disorder and their parents didnt have it (2) |
|
Definition
| they had a spontaneous mutation or reduced penetenerance in their parent |
|
|
Term
| why does a certian disorder or mutation become autosomal dominant (2) |
|
Definition
issue with receptor or scaffolding protein, metabolic pathway regulators
non-enzyme
example: if some collagen is junk but some is fine when they get put in mesh it sucks even if one parent donated good collagen |
|
|
Term
| what is the cause of autosomal recessive diseases |
|
Definition
| genes coding metabolic pathway participants (enzymes) are mutated |
|
|
Term
| what are some common patterns in autosomal recessive riseases |
|
Definition
skipps generations
complete penetrance is common and onset is usually earlier in life
inscest sometimes seen |
|
|
Term
| why do enzymes mutations cause recessive disorders |
|
Definition
| can still meet demant (upregulating or down regulating) with the good enzymes from one parent |
|
|
Term
| are sex linked disorders recessive or dominant |
|
Definition
| recessive. the dominant ones are so rare we dont study them |
|
|
Term
| what are the y-linked disorders |
|
Definition
|
|
Term
| how can x-linked disorders be identified on a pedigree |
|
Definition
mother is a carrier, son is affected
affected father doesnt have affected son |
|
|
Term
| why would a female get symptoms in a x-linked disorder |
|
Definition
| lionization (silencing of one X) |
|
|
Term
| what is the mutation in marfans syndrome, how does this cause disease |
|
Definition
fibrillin-1 (FBN1) mutation of connective tissue
microfibrils in ECM are made of tropoelastin and fibrillin making elastic fibers that are now weak
fibrillin usually sequesters TGF-B and keeps it inactive so now it is running around in the active form |
|
|
Term
| where are the elastic fibers tmost effected in marfans syndrome (3) |
|
Definition
| aorta, ligaments, ciliary zonules of the lens |
|
|
Term
| how is marfans acquired, what is the prevlence |
|
Definition
dominant 75%
spontaneous mutation 25% |
|
|
Term
| what does TGF-B usually do |
|
Definition
| released by proteases in injury to activate fibroblasts and cause re-epithelization |
|
|
Term
|
Definition
| constitutive activation of TGF-B receptor |
|
|
Term
| why does everyone with marfans present a little differetly |
|
Definition
| there are over 500 types of FBN1 mutations |
|
|
Term
| what systems have the most symptoms of marfans |
|
Definition
| skeletal, eye, cardiovascular |
|
|
Term
| what are the 5 general skeletal deformities of marfans |
|
Definition
arachnodactyly
hyperextensibility of joints
spinal deformities
chest deformities
high arched palate with crowded teeth |
|
|
Term
| what is arachnodactyly, what disease is it seen in |
|
Definition
marfans
elongated body shape with abnormally long legs, rms, fingers |
|
|
Term
| what spinal deformities do people with marfans have (3) |
|
Definition
| kyphosis, scoliosis, rotation or slipping of vertebrae |
|
|
Term
| what 2 chest deformities can people with marfans hae |
|
Definition
pectus excavatum
pigeon breast deformity |
|
|
Term
| what symptoms occur in the eye of people with marfans |
|
Definition
| bilateral dislocation or subluxation of the lens (ectopia lentis): in one eye it is ok but in both suspect marfans |
|
|
Term
| cardiovascular symptoms of margas (3) |
|
Definition
mitral valve prolapse causes congestive cardiac failure
dilation of the ascending aorti causes aortic incompentence an aortic dissecetion (common cause of death) |
|
|
Term
| what is the cause of eher's danlos syndrome |
|
Definition
they all have different causes leading to different symptoms
basically a disorder of the connective tissue that is due to a mutation affecting collagen synthesis or structure
not all are dominant either |
|
|
Term
| what are the common symptoms of elher danlos syndromes |
|
Definition
| skin, ligaments, and joints are hyperextensible and vulernable to trama and hypermobile and predisposed to dislocation |
|
|
Term
| explain normal LDL metabolism (long story) |
|
Definition
hapatocyte pumps out cholesterol complexed with TG or APO protein and this is called a VLDL
once it gets to the blood and muscle. muscle removes TG and uses it leaving IDL in the blood.
50% of IDL is recycled back to the liver via LDL binding receptors
the ret is converted to LDL
75% of the LDL goes back to the liver via LDL receptors
25% of LDL is taken into macrophages and smooth muscle cells causing athlerosclerosis |
|
|
Term
| explain the life cycle of a LDL receptor (5) |
|
Definition
made in the ER
shuttled to the golgi
transported to the membrane
phagocytose cholesterol through interaction with its substrate
recycled back to the cell then to the membrane again |
|
|
Term
| what causes familial hypercholesterolemia, how does this cause disease (3) |
|
Definition
mutation of LDL receptor
it increases HMG CoA reductase - liver cell sees no cholesterol coming in because its LDL receptor is broken, it increases HMC CoA reductase to put more cholesterol into the blood because it thinks its too low
IDL isnt getting recycled so it is all shunted to LDL increasing athlerosclerosis
scaverenger receptors pick up the LDL causing more athlerosclerosis |
|
|
Term
| what are some signs of familial hypercholesteroemia (4) |
|
Definition
elevated cholesterol
premature athlerosclerosis
increased risk of infection
xanthomas
infarctions |
|
|
Term
| what determines the severity of familial hypercholestermia |
|
Definition
| if they have two alleles it is bad |
|
|
Term
| how can you tell it if someone is a heterozygote familial hypercholesterolemia (4) |
|
Definition
2-3x cholesterol elevation
asymptomatic until adult then develop xanthomas along tendon sheaths, premature athlerosclerosis |
|
|
Term
| how can you tell it if someone is a homozygote familial hypercholesterolemia (3) |
|
Definition
5x cholesterol elevation
cutaneous xanthomas by childhood
infarctions by 15 yo |
|
|
Term
| what is the most common mutation in familial hypercholesterolemia |
|
Definition
| type II: problem with transport of receptor to the cell surface. receptor is functional but it cant get to the cell surface |
|
|
Term
| what is the significance of pku in the medical community, who is it more common in |
|
Definition
first newborn screen available
most common in scandinavian dsecent |
|
|
Term
|
Definition
| lack of phenylalanine hydroxylase so you get hyperphenylalaninemia and PKU. phanalanine cannot be converted to tyrosine so phenylalanine and its metabolites build up |
|
|
Term
| what are the symptoms of PKU |
|
Definition
| mental retardation, impairment of motor or verbal skills, seizures, decreased pigmentation of hair and skin, eczema, mousy odor or urine |
|
|
Term
| why do people with pku get mental redardation and mousy odor |
|
Definition
| accumulation of phenylalanine and its metabolites are neurotoxins |
|
|
Term
| why do people with pku get decreased pigmentation |
|
Definition
pneylalanine is turned into tyrosine by phenalaine hydroxylase and tyrosine is turned into melanin.
no phenalanine no melanin |
|
|
Term
| what are the other types of PKU, how are they different |
|
Definition
non-pku hyperphenylalaninemia- distinguished from PKU with serum levels of phenylalanine
type II and III dont involve phenalanine hydroxylase but other parts in the pathway. these dont cause neurological symptoms or cause redardation.
will still test posutuve for pku but dont develop the disease. restrictive diet wont helpt for I and III |
|
|
Term
| what is the treatment of pku |
|
Definition
| dietary restriciton of phenylalanine |
|
|
Term
| what happens if an adult or child with pku eats phenylalanine |
|
Definition
kids with get mental retardation
adults with get depression and other psych symptoms
they both will get the rest of the symptoms |
|
|
Term
|
Definition
| mother with pku dosent follow their diet and their baby gets pku symptoms due to phenylalanine build up even though the baby dosent have the disease |
|
|
Term
| what is the cause of galactosemia |
|
Definition
| galactose-1-phosphate uridyl transferase (GALT) mutation causes galactose-1-phosphate (galactatol) to build up |
|
|
Term
| what are the 6 areas of damage of susceptability in galactosemia |
|
Definition
failure to thrive (vomiting and diarrhea)
hepatomeagly
cataracts
CNS alterations
aminoaciduria
increased frequency of fulminant E. coli septicemia |
|
|
Term
|
Definition
| early removal of galactose from diet for first 2 years of life |
|
|
Term
| how is galactosemia diagnosed (2) |
|
Definition
transferase assy of leukocytes, erythrocytes
antenatal enzyme assays from cultured amniocytes or chronic vili |
|
|
Term
| what causes hepatomeagly in kids with galactosemia (2), when does it occur |
|
Definition
liver enlargement due to fatty change causes cirrhosis
jaundice
devlops in 1st week of life |
|
|
Term
| what causes cataracts in kids with galactosemia, when does it occur |
|
Definition
galactitol in lens increases toxicity
develops in 1st few weeks of life |
|
|
Term
| what are the CNS signs in galactosemia (4), when do they occur |
|
Definition
| loss of nerve cells, gliosis, edema, mental retardation (within 6-12 mo) |
|
|
Term
|
Definition
| impaired amino acid transport in kidneys |
|
|
Term
| why do kids with galactosemia have increased susceptability to E. coli |
|
Definition
| depressed neutrophil bactericidal activity |
|
|
Term
| what is the cause of lysosomal storage diseases |
|
Definition
| inherited lack of lysosomal enzyme leads to accumulation of substrate in the lysosome |
|
|
Term
| GM2 gangliosidosis: cause, what disease |
|
Definition
accumulation of GM2 gangliosides
Tay sac's disease - problem with hexosaminidase A that forms active enzyme complex that breaks down GM2 gangliosides |
|
|
Term
| where are most GM2 gangliosides |
|
Definition
|
|
Term
|
Definition
| commonly ashkenazi jews (eastern european descent) |
|
|
Term
| what are three findings in tay sacs |
|
Definition
foamy ytoplasmic vacoules in neurons
myelin figures
cherry red spot |
|
|
Term
| why do people with tay sacs have foamy cytoplasm in neurons, how can you identify this |
|
Definition
| neurons are balooned with gangliocides, stain positive for fat (oil red stain) |
|
|
Term
| how do myelin figures look, how can you see them |
|
Definition
concentric whorls, like onion skin
visible by EM |
|
|
Term
| what causes the cherry red spot in tay sacs |
|
Definition
| palw swollen ganglion cells accumulating in the margins of the macula |
|
|
Term
| when does tay sachs show up, what are three signs, what is the outcome |
|
Definition
normal until 6 mo
motor and mental retardation, blindness, dementia
vegetative state and death by 2-3 yo |
|
|
Term
| niemann pick disease cause, who gets it |
|
Definition
accuulation of sphingomyelin or cholesterol in phagocytic cells and neurons
seen in ashenazi jews (not type C though) |
|
|
Term
| neimann pick type A: aka, cause |
|
Definition
severe infantile
mutation in sphingomyelinase causes accumulation of sphingomyelin in phagocytic cells |
|
|
Term
| neimann pick type A: morphology (6) |
|
Definition
seen in neurons and PHAGOCYTIC CELLS
foamy fat in cytoplasm, myelin figures, SPLENOMEAGLY, hepatomeagly, protruberant abdomen, cherry red spot |
|
|
Term
| where do the cells accumulate in type A neimann pick (5) |
|
Definition
| nodes, marrow, tonsils, lungs, neurons |
|
|
Term
| neimann pick type A: appears when, cause of death (3) and when |
|
Definition
normal until 6 mo, failure to thriba due to vomiting, fever, lymphadenopathy
die by age 1-2 |
|
|
Term
| what is the difference between type A and B neimann pick (3) |
|
Definition
type B has less severe deficiency in sphingomyelinase
type B has no CNS involvement
usually live until adult |
|
|
Term
| what is the problem in type C neimann pick |
|
Definition
NPC gene encodes proteins in cholesterol tracking and is mutated
cells accumulate choleserol and GM1 and GM2 gangliosides |
|
|
Term
| what are the symptoms of type C neimann pick (9) |
|
Definition
| fetalis, stillbirth, neonatal hepatitis, chronic progressive neurological damage, ataxia, supranuclear palsy, dystonia, dysarthia, psychomotor regression |
|
|
Term
|
Definition
| mutation in glucocerebrosidase gene causing accumulation of glucocerebroside in phagocytes causing them to activate and release cytokines (IL-2, 6, TNF) |
|
|
Term
| what is a gaucher cell, what does it look like |
|
Definition
phagocyte containing distended lysosomes filled with lipid (wrinkled tissue cytoplasm)
pathoneumonic |
|
|
Term
| what is the most common lysosomal storage disease, what are the three types which is the most common |
|
Definition
gaucher's disease
chronic non-neuropathic form - most common
types I-III |
|
|
Term
| signs of type I gaucher's disease (4) |
|
Definition
hepatosplenomeagly, skeletal lesions (wide ephysis), NO BRAIN INVOLVED
decrease in life expetency |
|
|
Term
| why does type I gaucher;s get skeletal lesions |
|
Definition
| macrophages are sruffed with cholesterl and gangliosides and accumulate |
|
|
Term
| who gets type I gaucher;s |
|
Definition
|
|
Term
| when do people realize they have gaucher's - why |
|
Definition
| 60-70s they develop anemia |
|
|
Term
| what causes type II gauchers, when does it start, what is the prognosis, who gets it |
|
Definition
| no neuro signs or symptoms, symptoms start before 2 yo, early death, no jewish connection |
|
|
Term
| type III guachers: severity in comparison, symptoms, onset |
|
Definition
intermediate to I and II
CNS symptoms begin in teens and 20s |
|
|
Term
| what is the difference in the MOA of type I between II and III gauchers |
|
Definition
II and iii dont store glucosyleramide in neurons
accumulations in vessels becomes toxic to neuronal tissue |
|
|
Term
| what causes mucopolysaccharidosis, what organs does it involve (4) |
|
Definition
defective degredation of mucopolysaccharides
many organs including; liver, spleen, heart, vessels |
|
|
Term
| what causes the pathology in mucopolysaccharidosis (2) |
|
Definition
accumulations in phagocytes, endothelial cells, smooth muscle cells, and fibroblasts cause baloon cells
lysosomes in neurons may contain myelin figures |
|
|
Term
| what are the common symptoms of the mucopolysaccharidosis (6) |
|
Definition
hepaosplenomeagly ****
skeletal deformities - coarse facial features
valvular lesions
subendothelial deposits in coronary arteries, vessels and brain
corneal clouding
mental retardation |
|
|
Term
| what causes glycogen storage diseases, what areas of the body do these most effect and why |
|
Definition
mtation in enzymes involved in synthesis or degradation of glycogen
liver and skeletal muscle have the most glycogen |
|
|
Term
| what are the three types of glycogen storage diseases |
|
Definition
| hepatic, mypoathic, other |
|
|
Term
| what causes hepatic glycogen storage diseases, name of disease, 2 symptoms |
|
Definition
von kerke (type I glycogenosis)
deficiency of liver glycogen and metabolism enzymes (glucose 6 phosphatase)
hepatic enlargement, hypoglycemia |
|
|
Term
| mypoathic glycogen storage disease: cause, 3 signs and why, name of disease, deficient enzyme |
|
Definition
McArdle disease (type V glycogenosis)
phosphorlyase enzyme in glycolysis is broken
muscle weakness: impaired energy
muscle cramps after exercuse
no increas in lactate after exercise |
|
|
Term
| what 2 glycogen storage diseases cause early death |
|
Definition
pompe disease (type II glygogenosis)
brancher glycogenosis (type IV glycogenosis) |
|
|
Term
| pompe disease: cause and a symptom |
|
Definition
| lack of lysosomal acid maltase leads to storae of glocogen in lysosome, cardiomeagly |
|
|
Term
| brancher glycogenosis: cause, 3 symptoms |
|
Definition
deficiency of branching enzyme for glycogen
abnormal form of glycogen damages heart, liver, and muscle |
|
|
Term
| alkaprotonuria: claim to fame, cause |
|
Definition
first human inborn error of metabolism to be discovered
lack of homogentisate 1,2-dioxygenase 9HGO_ blocks metabolism of phenylalanine-tyrosine at level of hypogentistic acid (HA) |
|
|
Term
|
Definition
hypogenistic acid (HA) accumulates in urine and oxidizes to bensoquinones turning black
onchronosis: causes blue black pigment in connective tissues (ears, nose, cheeks, sclera)
deteroiration of cardiac valces (coronary artery calcification)
kidney stones due to HA build up
degenerative arthopathy similar to osteoarthritis appears in 30s |
|
|
Term
| what is the normal purpose of a trinucleotide repeat |
|
Definition
| CG rich region due to how nucleotides base pair abnormally (g-g). this stops DNA polymerase and in repair process youo get repeats and expansion |
|
|
Term
| where are trinucleotide repeats located in the genome (3) |
|
Definition
| intron, extron, untranslated regions |
|
|
Term
| how can you identify a nucleotide repeat region, what symptom are most repeats associated with |
|
Definition
| CG rich, neurodegenerative changes |
|
|
Term
| what region is a huntington disease repeat in, when does it happen |
|
Definition
| exon reagon dueing spermatogeneis |
|
|
Term
| what region is a fragile-x repeat in, when does it occur |
|
Definition
| untranslated region during oogenesis |
|
|
Term
| fragile x syndrome: inheritance, cause |
|
Definition
x-linked recessive
FRM1 normal trinucleotide repeat is expanded and AMPLIFIED over generations during oogenesis until one generation is long enough to cause the disease |
|
|
Term
| what repeat is involved in fragile x, where is it |
|
Definition
| CGG repeats in the 5'UTR region |
|
|
Term
| what does it mean if someone has pre-mutated fragile x syndrome, what are some symptoms |
|
Definition
| someone has a lot of repeats but not enough to cause full fragile X syndrome. these people have 30% chance of ovarian failure or 33% chance of intention tremor, cerebellar ataxia, and parkinsonism in men |
|
|
Term
| who many repeats does someone need to have a pre-mutation and how many to have fragile-x syndrome |
|
Definition
52-200 for premutation
200-4000 for fragile x |
|
|
Term
| what causes the pathology in fragile x syndrome |
|
Definition
| expansion areas are hypermethylated which spreads to the promoter and silences the region from transcription. so although the protein would be normal, it is not created |
|
|
Term
| what does the FMRI gene usually do |
|
Definition
| shuttle RNA to its final translation location in axons and dentrites |
|
|
Term
| how can fragile x be identified on a karyotype |
|
Definition
| chromosome tip is contracted and looks like it is broken off |
|
|
Term
| what is the most common cause of mental retardation, what is the second |
|
Definition
trisomy 21 is first
fragile x is second |
|
|
Term
| explain who gets fragile x more, male or females |
|
Definition
| males get it more because it is x linked but 50% of female "carriers" auctally have the disease due to lyonization |
|
|
Term
|
Definition
| certina pieces of chromosomes are silenced. it isnt the same x in every cell (mosaic) |
|
|
Term
| what are three common symptoms of fragile x |
|
Definition
facial dysmorphism: large mandible and ears
macro-orchidism (in 90%) |
|
|
Term
| how do you get a mitochonrdial disorder (2) |
|
Definition
| 100% of mitochondria come from mom but some mitochondrial proteins are coded for in the nucleus |
|
|
Term
| why are mitochondrial disorders heterogemic |
|
Definition
| not all mitochondria will transfer from the mom to kid cell, not all mitochondria will ahve the mutation so you need a lot of them to cause the disease |
|
|
Term
| what organisms are most dependent on the mitochondria, what kid of defects will a mitochondria issue cause, why |
|
Definition
CNS, skeletal muscle, liver, kidneys
issue causes deleterious defect on the organs because the enzymes of oxidative phosphorlyation (aerobic respiration) are messed up |
|
|
Term
| what disease is associated with a mitochondrial mutation |
|
Definition
| leber hereditary optic neuropathy (LHON) |
|
|
Term
| what are the signs of LHON (2), when does it occur |
|
Definition
progressive bilateral loss of central vision
leads to blindness
occurs between 15-35 yo |
|
|
Term
| what are some signs on a pedigree that can help identigy mitochondrial disorder (2) |
|
Definition
all moms kids have it
all the male children have no kids with it |
|
|
Term
| what is the normal function of methlyation in genes |
|
Definition
| deactivates genes, especially important in development |
|
|
Term
| what is genomic imprinting |
|
Definition
epigenetic process where a gene is inactivated during gametogenesis
on one parent the gene is silenced and the other parent has an active gene |
|
|
Term
| what combination of genes causes prader willi syndrome |
|
Definition
kid was supposed to get an active gene from dad and silenced gene from mom.
dads gene was deleted and now kid dosent get any gene (one deleted one silenced)
on CH15 |
|
|
Term
| what are the signs of prader willi syndrome(5) |
|
Definition
mental retardation
short stature
hypotonia (floppy baby)
obesity (hyperphagia)
hypogonadism |
|
|
Term
| what combination of genes causes angleman syndroome |
|
Definition
the kid was supposed to get an active gene from mom and a silenced (imprinted) gene from day on CH15
something happened in oogenesis to mom's chromosome and the gene was deleted now the kid has no gene (one gene from dad that is silenced, no gene from mm) |
|
|
Term
| what are the signs of angleman syndrome (4) |
|
Definition
| mental retardation, ataxic gait, seizures, inappropirate laughter |
|
|
Term
| what is another name for angleman syndrome |
|
Definition
|
|
Term
| when do kids with angleman syndrome learn to walk, why |
|
Definition
| ataxia pushes walking to 5-6 yo due to coordination issues |
|
|
Term
| what is a cytogenetic disorder |
|
Definition
| whole chromosome derangement, things that affect the karyotype |
|
|
Term
| what cytogenic disorders are compatiable with life (4) what are their names |
|
Definition
trisomy 13: patau syndrome
trisomy 18: edwards syndrome
trisomy 21: down syndrome
sex chromosome abnormalities (not only Y though)
these can still spontaneously abort |
|
|
Term
| when older men have children what problems occur |
|
Definition
| single gene defects like autism |
|
|
Term
| when older women have children what problems occur |
|
Definition
| non-dysjunction like trisomy 21 |
|
|
Term
| what age does the maternal risk for miscarriage increase and fertility decrease |
|
Definition
|
|
Term
| what are the signs of down syndrome (12) |
|
Definition
mental retardation
epicanthic folds making flat face
abundant neck skin
simian crease on hands
congenital heart defects
intestinal stenosis
umbilical hernia
predisposition to leukemia and infection
hypotonia
gap between first and second toe
large protrubrent tongue
later in life: neurodegeneration (alzheimers) |
|
|
Term
| what are the signs of edwards syndrome (10) |
|
Definition
prominent occiput
mental retardation
micrognathia
low set ears
short neck
overlaping fingers
congenital heart defect
renal malformations
limited hip abduction
rocker bottom feet |
|
|
Term
| what are the signs of patau syndrome (9) |
|
Definition
microphthamia
cleft lip and palate
mental retardation
microcephaly
polydactyly
cardiac defects
umbilical hernia
renal defects
rocker bottom feet |
|
|
Term
| are the three types of down syndrome and their abbreviations |
|
Definition
trisomy 21: 47XX +21
mosaic: 46XX/47XX +21
robertsonian translocation: 45XX -14 -21 +t(14q21q) |
|
|
Term
| what are the type types of edwards syndrome, what are their abbreviations |
|
Definition
trisomy 81: 47XX +18
mosaic: 46XX/47XX +18 |
|
|
Term
| what are the two types of patau syndrome, what are their abbreviations |
|
Definition
trisomy 13: 47XX +13
mosaic: 46XX/47XX +13 |
|
|
Term
| what is the most common cause of trisomy 21 |
|
Definition
| noondisjunction in gameotgenesis (95% of the time the extra chromosome comes from mom) |
|
|
Term
| what is the second most common cause of down sndrome, what happens |
|
Definition
robertsonian translocation: inherited
long arm of 21 translocates to 14 and short arm of 14 leaves because it is argocentric (one short and one long arm) and the short arm is full of junk dna |
|
|
Term
| why do robenson translocations have a high spontaneous abortion rate |
|
Definition
| because out of 6 possible combinations of egg chromosomes with normal sperm chromosomes 3 cause abortion, 1 causes a carrier, and 1 causes down syndrom |
|
|
Term
| how is a mosaic down syndrome created |
|
Definition
nondisjunction of Ch21 during embryogenesis
most cells will have a normal CH count so symptoms are variable |
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Term
| what causes the symptoms of down synfrom |
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Definition
| two genes are encoding NFAT (nuclear factor of activated T cells) a transcription factor that regulates genes in developmental pathways |
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Term
| what causes death of children in down syndrome (3) |
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Definition
| cardiac malformations (mostly), susceptability to leukemia and infection |
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Term
| what causes death of adults in down syndrome, what is the median age |
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Definition
47 yo
dementia, neurochemical like alzheimers |
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Term
| what is a cytogenic disorder that involves autosomes |
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Definition
| chromosome 22q11.2 deletion syndrome (DiGeorge) |
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Term
| what causes chromosome 22q11.2 deletion syndrome, what causes pathogenesis |
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Definition
deletion of a band of section 11 from long arm of CH22
deleted area contains a transcription factor for a gene |
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Term
| how is chromosome 22q11.2 deletion syndrome diagnosed |
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Definition
FISH: flourescent in situ (in tissue) hybridization
uses control and chromosome 22q11.2 gene probe |
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Term
| why are the symptoms of chromosome 22q11.2 deletion syndrome viarible |
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Definition
| they depend on the extent and location of the deletion |
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Term
| what are the signs of chromosome 22q11.2 deletion syndrome (7) |
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Definition
congenital heart defects
palate abnormalities
facial dysmorphism
developmental delay
T cell immune deficiency
hypocalcemia
psychosis/schizophrenia
(CATHC 22): cardiac defect, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia |
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Term
| what is DiGeorge disease, what symptoms define it |
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Definition
| it is a chromosome 22q11.2 deletion syndrome that has mostly T cell deficiency and thymus and parathyroid descention issues (causing hypocalcemia) |
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Term
| what is velocardiofacial syndrome, what symptoms define it |
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Definition
a chromosome 22q11.2 deletion syndrome
cardiac defects, dysmorphology |
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Term
| what are two general issues with sex chromosome disorders |
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Definition
| sexual development and fertility |
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Term
| when are sex chromosome disorders usually diagnosed |
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Definition
| puberty because they are difficult to diagnose at birth |
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Term
| how are extra X or Y chromosomes tolerated |
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Definition
| Y is tolerated but X causes mental retardation when it increases |
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Term
| what are 3 sex chromosome disorders |
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Definition
klinefelter syndrome
turner syndrome
XYY males |
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Term
| what is the cause of klinefelter syndrome (2) |
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Definition
at least 2X and 1Y, usually 47 XXY due to non0disjunction in gametogenesis because of mom or dad
some are mosaics 46XY / 47XXY |
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Term
| what causes pathogenesis in klinefelter syndrome |
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Definition
| genes on extra X escape inactivation as occurs in normal females and leads to feminization |
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Term
| what are signs of klinefelter (8) |
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Definition
hypogonadism: atrophy (common)
sterlity
elongated eunuchoid bodies (feminine)
reduced body hair
gynecomastia: increased risk of breast cencer
greater risk of extragonadial germ cell tumors and SLE (like in women) |
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Term
| what is the cause of turner syndrome (2), which is worse |
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Definition
partial or complete monosomy of short arm of X chromosome
some are 45X: father produces sperm without a sex chromosome (more severe)
some have abnormalities in the X so they appear normal and have amenorrhea |
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Term
| what are the signs of tuner syndrome |
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Definition
neck webbing
puffy hands or feed
short stature
primary or secondary amenorrhea
sterlity
antibodies to thyroid (hypothyroidism) in 50%
cardiovascular abnormalities |
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Term
| why do people with turner syndrome have a webbed neck |
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Definition
| cystic hygroma (increased fluid behind the neck) due to heart issue increases chance of birth defects and if persists it causes increased skin in the area |
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Term
| what is the most common cause of death in kids with turner syndrome |
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Definition
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Term
| what heart problems are seen in turner syndrome (2) |
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Definition
hypoplastic left heart
coarctation of the aorta |
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Term
| what are the symptoms of a XYY male (2) |
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Definition
| taller stature, cystic acne |
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