Molecular,Biochem,Cellular Basis of Genetics 2 Flashcards
What causes Acute Intermittent Porphyria?
Its caused by mutation in the gene encoding for porphobilinogen deaminase (PBGD)
What kind of inheritance is Acute Intermittent Porphyria?
Autosomal Dominant
What causes Acute Intermittent Porphyria to show symptoms?
When heme levels drop in hepatocytes
How is Acute Intermittent Porphyria exacerbated?
Barbituates (Drugs)
Steroids
reducing diets
surgery
What happens if exposed to precipitating factors?
increase of synthesis of P450, dropping heme levels and reducing the heme synthetic pathway also, via feedback inhibition of heme on δ-amino-levulinic acid (ALA) synthetase
What is the clinical presentation of Acute Intermittent Porphyria?
acute episodes of a variety of gastrointestinal and neuropathic
symptoms; between episodes, the patient is healthy
Abdominal pain is the most common symptom (Vomiting)
Mental disturbance: (Confusion, Emotional upset, Hallucinations and psychosis)
What is Familial Hypercholesterolemia?
is one of the type 2 familial hyperlipoproteinemias characterized by elevation of plasma cholesterol carried by LDL.
What is the inheritance of Familialhypercholesterolemia?
Autosomal Dominant
What is damaged in Familialhypercholesterolemia?
Mainly LDL receptors
4 possible proteins may cause Hypercholesterolemia or Hyperlipidemia
What are the four proteins associated with Familialhypercholesterolemia?
- LDL receptor mutation: Chromosome 19
- Mutations in the LDL receptor binding domain of ApoB-100: Chromosome 2
- impairs LDL binding to its receptor by ApoB-100
- PCSK9 protease activity leads to degradation of the LDL receptor: Ch 1
- Mutation in ARH adaptor protein,
- links the receptor to the endocytic machinery of the coated pit causing clustering of the LDL receptor-ApoB-100 complex in clathrin-coated pits: Ch 1
What is the most important gene abnormality in FamilialHypercholesterolemia? Why?
PCSK9 protease gene
Mutation of this gene will cause the disease but some variants lower the plasma LDL cholesterol level giving some protection from coronary hearts disease
What are some symptoms of Familial Hypercholesterolemia?
premature heart disease
xanthomas (homozygous for the gene)
arcus corneae (fat deposits in cornea)
What is deficient in Cystic Fibrosis?
pancreatic enzymes
How do you restore normal digestion in Cystic Fibrosis?
pancreatic enzyme supplement
What is wrong with Cystic Fibrosis males?
They lack a vas deferens and therefore are infertile
How is the stool of CF patients?
Greasy, lighter in color,
What is the major cause of Cystic Fibrosis?
Psudomonas aeruginosa
What are the 2 muscular dystrophies resulting from defects in dystrophin gene?
- Duchenne
- Beckers
What type of inheritance is Duchenne and Beckers?
X-Linked
What are the clinical features of Duchenne muscular dystrophy?
- gower maneuvers
- High lvs of creatinine kinase (CK)
- boys are normal first year of life
- slow developing progression of muscle weakness
- gait
- lumbar lordosis
- Wheelchair bound by age 12
- joint contracture
- pseudohyperthrophy: increase in the size of calf (calf muscles replaced by fat and fibrous connective tissue)
Greatly elevated Creatinine levels may indicate what disease?
Duchenne Muscle Dystrophy
What are the clinical features of Becker’s Muscle Dystrophy?
sames as Duchennes but at a slower onset
Genetically, Duchenne and Becker’s exemplify what?
Allelic Heterogeneity (different mutation same gene)
Deletions in the codon for Duchenne MD is due to what?
a frameshift mutation
Deletions in the codon for Becker’s MD is caused by?
In-frame mutation
What is the frequency for DMD and Becker’s?
60%
What is Ehrler-Danlos Syndrome?
genetic defect in collagen structure, synthesis, secretion,
or degradation.
What is the clinical presentation of Ehrler-Danlos?
Hypermobility
Hyperelasticity
Skin fragility
Tendency to bleed
Aortic Aneurysm
Cigarette Paper skin
What do Type 1 and Typer 2 Ehrler-Danlos have in common?
The mutations are linked to loci that contain the COL5A1 gene or COL5A2 genes; encoding the alpha chains of type V collagen, leading to defective type V collagen
What is the frequency of Type 1 and 2 Ehrler-Danlos Syndrome?
1/30,000
What is the frequency of Type 3 Ehrler-Danlos Syndrome and how does it presents?
1/5,000
Patient may have arterial or uterine rupture
What type of collagen is associated with type 4 EDS and where would you find it?
Reticular Type 3 Collagen
Found in vasculature and skin
What is the deficiency found in type 6 EDS?
Lysyl Hydroxylase
Whats wrong in Type 7 EDS?
Can’t turn procollagen to collagen
With what can we associate type 8 EDS?
Dermatosporaxsis
skin fragility
Of the two dystrophies resulting from a mutation in the dystrophin gene, which is more severe?
Duchenne: more severe/lack of dystrophin
Beckers: less severe
What is the defect gene in Ehrler-Danlos Syndrome?
Col3A1
What is the major risk with type 3 Ehrler-Danlos Syndrome?
Death
