Unit 7 - Introduction to Medical Genetics Flashcards Preview

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Flashcards in Unit 7 - Introduction to Medical Genetics Deck (20):
1

inherited VS acquired disease

inherited gene complement - mutations may be transmitted from one or both parents (constitutional genome)
-present since birth

acquired gene complement - subset of cells in an individual that arose by clonal propagation from a single mutation in one cell
-arises later in life

2

what is a syndrome?

set of characteristics which occur together and are assumed to have a common basis
-not all characters occur in all affected individual
-range of variability within a population

3

what is biochemical genetics?

subspecialty of genetics that deals with diagnosis, treatment, and research of inborn errors of metabolism

4

what are inborn errors of metabolism?

genetically determined biochemical disorder where a specific enzyme defect produces a metabolic block
-accumulation of substrate
-deficiency of products

5

alcaptonuria

accumulation of homogentisic acid due to defect in homogentisic acid oxidase in blood damages cartilage, heart, and kidney

6

what causes albinism?

defect in tyrosine oxidase prevents pigment formation
-can be complete (no pigment in any organ/tissue, plus red eyes) or partial (some organs or tissue have pigment)

7

what are 3 types of hyperphenylalaninemias?

phenylketonuria
variant PKU
defects in BH4

related to function of phe hydroxylase

8

when does PKU occur?

AR mutation of phe hydroxylase (PAH) prevents phe --> tyr, causing phe accumulation
-small fraction of phe is converted to phenylpyruvic acid to be detected in urine
-must be treated early and in pregnancy by diet modification
--even if fetus is non-PKU, mother's exccess PKU can cross placenta and damage fetus

9

what is non-PKU hyperphenylalaninemia?

10x increase in phe levels (decrease in phe hydroxylase, but still functional)
-less damaging, may be benign
-may not require special diet

10

variant PKU

between full PKU and non-PKU hyperphenylalaninemia
-requires diet, but not as restrictive as PKU patients

11

defect in BH4 metabolism

1-3% of hyperphenylalaninemia patients
-non-mutant phe hydroxylase gene, but mutant DHPR gene (qBH4 --> BH4)
-patients don't completely respond to PKU diet and develop neurological defects
-thus, supplement with oral BH4 for PAH problem, and L-dopa or OH-trp for sopamine/NE/E and serotonin pathways, respectively

12

lysosomal storage diseases

recessive due to mutation of lysosomal hydrolytic enzyme that leads to failure of degradation and accumulation of macromolecules in lysosomes
-over 50 known deficiencies, and clinically heterogeneous
-common presentation is progressive degeneration as organelles become larger, so affected organs/tissues increase in mass

13

how does GM2 gangliosidoses come about?

lysosomal storage disease; 3 genes make 3 PRO that function together
-alpha, beta subunits (come together to form dimer) and activator protein)

14

Tay Sachs disease?

AR, onset of 3-6 mo, and death in 2-4 years
-deficiency of hexosaminidase A, unable to degrade GM2 ganglioside
-no known treatment, so GM2 builds up in lysosomes and die between 2-4 years
-have cherry red spot in retina of eye

15

mucopolysaccharidoses symptoms and cause

group of heterogenous disorders
-absence of specific enzyme involves in degradation of glycosaminoglycans
-accumulation of macromolecules in lysosomes
-most are AR, but Hunter syndrome is XLR
-permanent, progressive damage
-short stature, delay, skeletal abnormalities, joint stiffness, thickened skin, heart/liver/spleen damage
-some diseases are more severe than others, are progressive, and worsen over time

16

treatment for mucopolysaccharidoses

-bone marrow transplantation
-enzyme replacement therapy
-gene therapy

17

osteogenesis imperfecta symptoms and cause

due to mutations in type I collagen with either reduced collagen production or defective collagen
-4 major classes that range from mild to lethal, all AD
--I - mildest; reduced collagen production (collagen made in half the normal quantity, causing brittle bones)
--II - perinatal lethal
--III - between II and IV
--IV - mild to moderate bone deformity and fracturing
-major character is brittle bones and skeletal deformities

18

Ehler-Danlos syndrome

error in post-translational modification of collagen (primarily COL5A or COL3A genes) with multiple subtypes (AD, AR, and XLR)
-have fragile skin, joint hypermobility, and skin hyperextensibility

19

Marfan syndrome symptoms and causes

connective tissue disorder of fibrillin gene
-primary targets are skeleton, heart, lungs, and eyes
-tall and thin, with very long fingers, joint laxity, and scoliosis
-lung problems cause pneumothorax
-dislocation of lens or myopia are common findings
-cataracts, glaucoma, and retinal detachment are additional problems
-heart issues include mitral valve prolapse, dilatation, and dissection of aorta (common death cause is rupture of thin aorta)

20

Marfan syndrome treatment

no known cure, but effective management
-know limits, limit stress
-surgical repair of aorta is possible
-orthopedic braces and devices help skeletal issues, and there are well-established management programs for eye problems