Term
| What are the 2 diseases involved in mutations of structural proteins? |
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Definition
| Marfans Syndrome and Ehlers-Danlos Syndrome |
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Term
| Marfan Sydrome: mutation in what? |
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Definition
a mutation in structural protein fibrillin (in gene FBN1) that is needed in many connective tissues
-AUTOSOMAL DOMINANT |
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Term
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Definition
1. Skeletal muscle manifestations: long, slender limbs, long fingers
2. Cardiac manifestations: aortic aneurysm: a normal aorta has lots of elastic fibers (=fibrillin), so the aneurysm dilates and leads to tear in aorta.
-also can causes mitral valve incompetence: the posterior leaf is big and closes and balloons up into atrium. It is possible for the chordae tendenae to rupture
3. Ocular: subluxation of eye lens |
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Term
| Ehlers-Danlos Syndrome: what is the mutation? |
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Definition
-AUTOSOMAL DOMINANT
-mutation in structural protein collagen
-There are different subtypes of ED, in subtype 4: collagen in color, digestion is then abnormal. In subtype 6: occular abnormalities
-glysyl hydroxylase is involved in this: synthesis of collagen (cross links collagen) |
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Term
| Sx of Ehlers-Danlos Syndrome |
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Definition
-unhealing contusion on face of baby, extra "stretchy" skin on back of head
-hyperextended joints
-subtype 1: diaphragmatic hernias=critical |
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Term
| What is the receptor protein mutation? |
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Definition
| Familial Hypercholesterolemia |
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Term
| Mutation of Familial Hypercholesterolemia |
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Definition
-mutation in gene that specifies receptor protein for LDL on liver membrane
-LDL isn't taken up and metabolized into lysosomes in liver = so level increases in blood
-LDL normally binds to its receptors and converted to lysosome (metabolized) =but can't do this
-if HETEROZYGOUS: 2-3 fold increase in LDL (later onset)
-if HOMOZYGOUS: over 5 fold increase of LDL in blood
-AUTOSOMAL DOMINANT |
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Term
| Sx of Familial Hypercholesterolemia |
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Definition
-usually in young people: when there is a HIGH level of LDL
-plaque build up in arteries and leads to arteriosclerotic disease quickly |
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Term
| What are the two enzyme protein mutations we discussed? |
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Definition
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Term
| Phenylketouria (PKU) is caused by what mutation? |
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Definition
-a mutation in the enzyme phenylalanine hydroxylase that transfers phenylalanine to tyrosine
-phenylalanine builds up in blood |
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Term
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Definition
-in infants, can be known to vomit repetitively, restlessness, skin rash
-MOUSY urine smell
-Sx can arise earlier than first screening comes back (after birth) within a week.
-if untreated, severe Sx: severe mental retardation, mousy odor, dermatitis, unpigmented skin and hair
-if missed in critical time (within 6months severe sx arise)
-easily controlled: eat foods without phenylketones
-child bearing female with PKU: intending to get pregnant should watch diet bc fetus cannot handle it. This is "pre-conception dietary management"
-about 10% cannot be treated with diet change |
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Term
| What mutation occurs with Galactosemia? |
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Definition
-mutation in gene that specifies enzyme galactose-1-phosphate uridyl transferase
-cannot break down galactose so substances made from galactose build up and effect liever, kidney, brain and eyes |
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Term
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Definition
-cirrhosis of liver
-splenomegaly
-cataracts of lens
-toxic intermediates poison renal tubules
-cerebral cortex loses neurons
-vomiting any MILK in first 2 days of life = BIG CLUE
-true diarrhea |
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Term
| Any type of Tx for Galactosemia? |
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Definition
-avoid milk for AT LEAST first 2-3 years of life bc this is when brain is "done" developing
-milk cannot be tolerated bc unmetabolized milk builds up |
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Term
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Definition
-test urine: a urine test for reducing substances (not glucose)
-Dx by amniocentesis during pregnancy |
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Term
| What are the four types of Lysosomal storage diseases and what happens? |
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Definition
-Tay-Sachs
-Niemann-Pick
-Gaucher's
-Mucopolysaccharidoses
=there is a build up of insoluble metabolites (toxic intermediates) |
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Term
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Definition
-gangliosides
-they build up in CNS/PNS and neurons are filled up with gangliosides
-known as "foamy cells" and lead to severe neurological dysfunctions:
-mental retardation
-blind
-progressive: death by age 2-3
-AUTOSOMAL RECESSIVE
-can dx prenatally: detection of heterozygous carrier |
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Term
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Definition
-caused by accumulation of sphingomyelinides
-there is a sphingomyelinase deficiency
-accumulates in: NS, liver, spleen, marrow
-sphengomyelinides build up in mononuclear phagocytes
-LARGE splenomegaly
-neurodeterioration/death in 5yrs |
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Term
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Definition
-caused by buildup of glucocerebrosides in endothelial system
-deficiency of glucocerebrosidase
-Gaucher's cells : like wrinkled tissue paper
-enlarged liver, distended abdomen |
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Term
| What are the 3 types of Gaucher's ? |
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Definition
Type 1: no neurological impairment and normal lifespan (99% of population)
Type 2: highly lethal, severe CNS impairment
-Type 3: intermediate in severity and is known to be juvenile-type
-children must have ENZYME replacement to treat |
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Term
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Definition
-7 types: depending on specific enzyme deficiency
-build up of different mucopolysaccharides
-accumulation of dermatan, heparin or keratan sulfates
-progressive disorders of different systems: liver, spleen, heart, BV
-typical coarse facial features=look more like each other than own family!
-delay developmentally |
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Term
| Glycogen storage diseases |
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Definition
-autosomal recessive
-deficiencies in glycogen synthesis/degradation
-12 forms fall in to 3 main categories:
-hepatic forms
-myopathic forms
-generalized glycogenoses |
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Term
| 1. Hepatic form of glycogen storage |
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Definition
| = hepatomegaly, hypoglycemia, liver cannot produce glucose in times of stress |
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Term
| 2. Myopathic forms of glycogen storage |
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Definition
| =enzyme lacking in skeletal muscle, causes cramping of muscle |
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Term
| 3. Generalized form of glycogen storage |
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Definition
| =systemic distribution, heart, CHF in 2 weeks |
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Term
| What are the mutations of growth regulatory proteins? |
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Definition
1. Familial neoplasia syndromes
2. Neurofibromatoses (2 types) |
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Term
| Type 1 Neurofibromatosis: von Recklinghausen's |
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Definition
-AD
-mutation in growth regulatory proteins causing neurofibromas found in PNS anywhere along peripheral nerve fiber |
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Term
| Sx of Neurofibromatoses type 1 |
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Definition
-multiple neurofibromas: fairly discrete, cutaneous stigmata
-cafe au lait spots
-pigmented dark spots/tumors in iris = Lisch nodules
-neurofibroma can grow in strategic areas: intercostal arteries (lead to fatal hemothorax), malignant transformation (often on neck)
-meningiomas |
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Term
| What's the gene with mutation for type 1 neurofibromatoses |
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Definition
=on chromosome 17: which encodes for negative regulator of RAS oncogene= which promotes unregulated growth.
-unlocks the oncogene, and promotes nerve cell unregulated growth |
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Term
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Definition
-very similar to type 1, but neurofibromas are bilateral
-chromosome 22 is location of mutation |
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Term
| Multifactorial inheritance |
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Definition
-number of different mutations inherited
-Diabetes
-HTN
-Schizophrenia
-Bipolar disorder
-no specific gene, but hereditary |
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Term
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Definition
-result of nondisjunction or mispairing
-abnormal # of chromosomes |
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Term
| Autosome cytogenic disorders: Trisomy (3 types) |
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Definition
Trisomy 13: Patau
Trisomy 18: Edward's
Trisomy 22: Downs |
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Term
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Definition
-Patau
-1 in 15000 born
-most are stillborn, ones that live will have cognitive disorders, squashed face |
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Term
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Definition
-Edward's syndrome
-1/8000
-bird-like face
-usually female |
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Term
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Definition
| -Down's syndrome -1/700 -alzheimers like dementia in 40s+ -40% will have cardiac issues |
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Term
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Definition
-deletion of part of p arm on chromosome 5
-Cri du Chat
-cat cry
-1/50000
-disjunction on maternal side |
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Term
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Definition
XXY, 47
-male
-tall, thin
-hypogonadism, testicular atrophy
-decreased facial/body hair
-high risk for testicular cancer |
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Term
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Definition
X, 45
-female
-1 in 3000
-mosciasm
-shorter
-neck webbing
-lympedema
-horse shoe kidney (only one)
-not fully functioning ovaries
-amenorrhea
-coarctation of aorta (narrowing just beyond arch which created HTN in upper extremities, can barely find pulse in lower )
-primary hypogonadism |
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Term
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Definition
| presence of 2+ populations of cells |
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Term
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Definition
p = short arm
q = long arm |
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Term
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Definition
| extra/deletion chromosome |
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Term
| Patterns of rearrangement |
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Definition
-translocation
-isochromosomes (split opposite way: 2 short arms, 2 long arms)
-deletion
-inversions (paracentric-one arm, pericentric-both arms) |
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Term
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Definition
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Term
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Definition
| 69+ chromosomes, usually results in spontaneous abortion |
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Term
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Definition
45, 47 chromosomes
-manifested as specific syndrome
-nondisjunction
-failure of pairing of homologous chromosomes
-autosomal monosomy is usually fatal |
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