Term
| What is the most common cause for familial hypertrophic cardiomyopathy? |
|
Definition
| Beta-Myosin Heavy chain (B-MyHC) (35-50%) |
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Term
| How do mutations involved in Familial Hypertrophic Cardiomyopathy cause ventricular hypertrophy? |
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Definition
| By enhancing contractile function. Recall, the more a muscle is used, the larger it becomes. |
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Term
| What is locus heterogeneity? |
|
Definition
Mutations in DIFFERENT GENES cause the same symptoms.
(ex: familial hypertrophic cardiomyopathy) |
|
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Term
| What do FGFs influence after binding to their receptor (FGFR)? |
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Definition
| cell proliferation, migration, differentiation. This is especially important in early development. |
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Term
| What gene is mutated in Achondroplasia? |
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Definition
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Term
| What substitution in FGFR-3 gene is responsible for achondroplasia? |
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Definition
G1138A = guanosine to adenine at position 1138 (98% of the time) this causes a glycine to argenine amino acid substitution at aa # 380 |
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Term
What kind of inheritance is familial Hypertrophic Cardiomyopathy? |
|
Definition
|
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Term
| What kind of inheritance is Achondroplasia? |
|
Definition
|
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Term
| What happens to individuals homozygous for the achondroplasia mutation? |
|
Definition
| It is lethal and they die before birth |
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Term
| What is the role of FGFR-3? |
|
Definition
An FGF receptor that negatively regulates bone growth. G380R mutation causes constitutive activation of receptor. This in turn promotes decreased bone formation. |
|
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Term
| How are Hypochondroplasia, Thanatophoric Dysplasia, and achondroplasia related? |
|
Definition
They are examples of allelic heterogeneity.
(mutations in the same gene cause different phenotypes) |
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Term
| What type of inheritance is Osteogenesis Imperfecta Type 1? |
|
Definition
|
|
Term
| What mutations in collagen type 1 are lethal? |
|
Definition
|
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Term
| What type of Osteogenesis Imperfecta is lethal and what substitution is involved? |
|
Definition
| OI type 2, glycine substitutions |
|
|
Term
| Which Osteogenesis Imperfecta is least severe? |
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Definition
|
|
Term
| Which Osteogenesis presents with Blue Sclera? |
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Definition
|
|
Term
| What role do glycines play in collagen? |
|
Definition
| They are necessary for the proper formation of the triple helix. |
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|
Term
| Which Osteogenesis Imperfecta presents with bowing femurs and tibias? |
|
Definition
|
|
Term
What does Osteogenesis type 3 present with? |
|
Definition
| Progressive deformity after birth |
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Term
| Is it worse to have a mutation in the C-Terminus or N-Terminus of a collagen gene? why? |
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Definition
| C-terminus because this is the location where triple helix formation is initiated. |
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Term
| In Osteogenesis type 1 is it worse to have the mutation in the a1 or a2 gene? |
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Definition
| a1 gene because it is expressed with 2x the level of a2, and therefore the effects of its mutation are more severe. |
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Term
| What disease is characterized by Hyperextensibility, Joint Hypermobility, and Connective Tissue Fragility? |
|
Definition
|
|
Term
| What type of inheritance is Ehlers-Danlos Syndrome type 1, 2, 4? |
|
Definition
|
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Term
| What type of collagen is mutated in EDS 1 and 2? |
|
Definition
|
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Term
| A patient presents with translucent skin, visible veins, but NO hyperflexibility of joints or skin. What is your diagnosis? what is mutated? |
|
Definition
Ehlers-Danlos Type IV.
Collagen type 3 |
|
|
Term
| What type of inheritance is EDS 6 and 7? |
|
Definition
|
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Term
| Which type of EDS is the most often lethal form of the disease? |
|
Definition
EDS type 4
(Vascular-Type EDS) |
|
|
Term
| What type of EDS is vascular-type EDS? |
|
Definition
|
|
Term
| Defects in Lysyl Hydroxylase cause which form of EDS? |
|
Definition
|
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Term
| Defects in conversion of type 1 procollagen to collagen are characteristic of which EDS? |
|
Definition
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Term
What specific defects create an inability to convert procollagen type 1 to collagen type 1 in EDS VII? |
|
Definition
1) Deletions of Exon 6 (cleavage site for N-protease) 2) Defect in N-Protease |
|
|
Term
| What associated cardiovascular problems are encountered with Marfan Syndrome? |
|
Definition
Aortic Aneurysm Mitral Valve Prolapse |
|
|
Term
| What inheritance pattern is Marfan Syndrome? |
|
Definition
|
|
Term
| What mutation is the most common cause of Marfan Syndrome? |
|
Definition
Fibrillin-1 gene mutation
*a Dominant negative mutation* |
|
|
Term
| What is the inheritance pattern for Hypophostphatemia? |
|
Definition
1)X-linked
2)Autosomal Dominant
3)Hereditary (?) |
|
|
Term
| What 3 genes are involved in hypophosphatemia? |
|
Definition
|
|
Term
| What is the role of NPT2? |
|
Definition
| It is a sodium-phosphorous cotransporter involved in phosphate absorption in the intestines and reabsoption in the kidneys |
|
|
Term
| What is the role of PHEX protein? |
|
Definition
| It is a protease that inactivates PNT, an inhibitor of NPT2 synthesis, thereby increasing NPT2 synthesis |
|
|
Term
| What is the role of FGF23? |
|
Definition
| An inhibitor of NPT2 synthesis, causing a decrease in phosphate absorption and low phosphate serum levels |
|
|
Term
| What results from a mutation in PHEX? What hypophosphatemia is this characteristic of? |
|
Definition
Decreased PHEX causes an increase of the NPT2-inhibitor PTN. Therefore, NPT2 is decreased, less phosphate is reabsorbed, and more is excreted by the kidney (phosphate wasting)
X-linked hypophosphatemia |
|
|
Term
a gain of function mutation in FGF23 prevents its proteolytic cleavage and therefore keeps its serum levels high. How does this affect Phosphate levels and why?
Of which Hypophosphatemia is this characteristic? |
|
Definition
increased FGF23 causes increased Inhibition of NPT2. Therefore, less phosphate is absorbed and more is excreted by the kidneys.
Autosomal Dominant Hypophosphatemic Rickets
(ADHR) |
|
|
Term
Loss of funtion mutations in NPT2 result in decreased phosphate absorption.
These mutations are characteristic of which type of hypophosphatemia? |
|
Definition
Hereditary hypophosphatemic rickets with Hypercalciuria
(HHRH) |
|
|
Term
| What type of inheritance does hemochromatisis display? |
|
Definition
|
|
Term
| What is the treatment for Hemochromatisis? |
|
Definition
Phlebotomy:
weekly removal of 500ml of blood. This will remove approximately 250mg iron until appropriate range is reached. Then, once every 3 months. |
|
|
Term
| What is HFE? what does it do? |
|
Definition
| A membrane protein in enterocytes. Regulates the amount of iron exporter (ferroprotein) and importer (DMT1) based on iron saturation of transferrin protein. |
|
|
Term
| What mutation is most often responsible for Hemochromatosis? |
|
Definition
C282Y mutation in HFE protein
(cysteine replaced by tyrosine causing misfolded, and thereby degraded protein product) Homozygous individuals for thismutation will develope HHC 80% of the time. |
|
|
Term
| What gene and protein are most commonly defective in Hereditary Spherocytosis? |
|
Definition
|
|
Term
| What is the treament for Hereditary Spherocytosis? |
|
Definition
|
|
Term
| Anemia, Jaundice, and Splenomegaly can indicate what genetic disorder? |
|
Definition
|
|
Term
| What is defective in Hereditary Elliptocytosis? |
|
Definition
Spectrin a-spectrin mutations cannot form aB heterodimers
b-spectrin mutations cannot form tetramers
(when spectrin tetramers are absent, cell stays elliptical) |
|
|
Term
| What is the clinical presentation of Epidermolysis Bullosa? |
|
Definition
| Blistering of skin even after slight contact |
|
|
Term
| Defects in the epidermal basal layer cause what variation of Epidermolysis Bullosa? |
|
Definition
|
|
Term
| Defects in the basement membrane cause which variation of Epidermolysis Bullosa? |
|
Definition
|
|
Term
| Defects in the subepidermal anchoring fibrils cause which variation of Epidermolysis Bullosa? |
|
Definition
|
|
Term
| What mutations are present in EB Simplex? |
|
Definition
| Keratin 5 and 14 mutations. |
|
|
Term
| What mutation is responsible for Junctional EB? |
|
Definition
|
|
Term
| What mutation is responsible for Dystrophic EB? |
|
Definition
|
|
Term
What cancer is often associated with Recessive-Type Dystrophic EB? |
|
Definition
| Squamous Cell Carcinomas (SCC) |
|
|
Term
| Squamous Cell Carcinoma is often associated with which form of Epidermolysis Bullosa? |
|
Definition
| Recessive-type Dystrophic EB |
|
|
Term
| Frequent Urination, Blood in the Urine, High Blood Pressure, and discomfort in the abdominal side are symptoms of which disease? |
|
Definition
| Polycystic Kidney Disease |
|
|
Term
| What genes are mutated in Polycystic Kidney Disease? |
|
Definition
PKD1 - encodes polycystin 1 PKD2 -encodes polycystin 2 |
|
|
Term
How do Polycystin 1 & 2 function? |
|
Definition
Both are located on cilia and involved in the activation of Ca++ channels.
They are also believed to play a role in the prevention of cell division. Once mutated, they promote cell division and the accumulation of fluid, causing cysts. |
|
|
Term
| Which polycystin gene is more commonly defective? |
|
Definition
|
|
Term
How is the PKD1 gene typically mutated? |
|
Definition
| Erroneous repair owing to the propensity of PKD1 gene to unwind and form a triple helix. RNA polymerase II makes an unnecessary repair and introduces a mutation. |
|
|
Term
| Hemartomas, Mental deficits, and Seizures are typical manifestations of which disease? |
|
Definition
|
|
Term
| What genes are responsible for PREVENTING Tuberous Sclerosis? |
|
Definition
TSC1 - Hamartin Protein TSC2 - Tuberin Protein these are tumor suppressor genes that inhibit cell growth. |
|
|
Term
| Which Tuberous Sclerosis preventing gene/protein is more commonly mutated? |
|
Definition
|
|
Term
| What is the protein pathway involving prevention of Tuberous Sclerosis? |
|
Definition
| Hamartin and Tuberin collectively inhibit Rheb. Rheb normally promotes mTOR, which promotes cell growth. Presence of Hamartin/Tuberin complex therefore prevents cell growth. Mutation in either Tuberin OR Hamartin will produce a non-functional complex and result in Tuberous Sclerosis. |
|
|
Term
| What type of genes are TSC1 and TSC2? |
|
Definition
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