Intro To Medical Genetics

Question 0

Mutations occur at

Answer 0

cytogenetic or molecular level

Question 1

A mutation is

Answer 1

Permanent, heritable change in sequence in DNA

Question 2

Mutations can be

Answer 2

Positive, negative, or neutral

Question 3

A syndrome is

Answer 3

a disorder with a set of characteristics that occur together and assumed to have a common basis.

Question 4

With syndromes there is a

Answer 4

range of variability, not all people have all characters

Question 5

Inborn errors of metabolism are

Answer 5

genetically determined biochemical disorders in which a specific enzyme defect produces metabolic block

Question 6

Inborn errors of metabolism are characterized by

Answer 6

accumulation of substrate and deficiency of products

Question 7

alcaptonuria

Answer 7

accumulation of homogentistic acid in the blood; damage to cartilage

Question 8

albinism is caused by a mutation in

Answer 8

tyrosine oxidase

Question 9

albinism can be

Answer 9

complete: no pigment in any organ or tissue

or incomplete: some organs or tissues have pigment

Question 10

When a substrate cannot be converted to normal product ___ can increase in activity. Why?

Answer 10

secondary pathways; can be salvage pathways to prevent build up of toxic substances

Question 11

Why can it be bad that enzymes may partake in more than one pathway?

Answer 11

a single deleterious mutation in such an enzyme can affect many processes negatively

Question 12

What are the characteristics of the inborn errors of metabolism?

Answer 12

• single enzyme defect
• recessive
• many recognized disorders
• challenge to detect the particular pathway and substance involved
• use biochem and genetics to make a diagnosis

Question 13

What are the common features of patients with biochemical disorders?

Answer 13

poor growth
mental retardation
problems in general metabolism
neurological problems

Question 14

What information can hint to biochemical dysfunction?

Answer 14

clinical picture, onset of MR over time, other affected siblings, unexplained infant deaths

Question 15

what are the hyperphenlalaninemias

Answer 15

phenylketonuria, variant PKU, and defects in BH4

all involve disorders in the function of phenylalanine hydroxylase

Question 16

phenylketonuria

Answer 16

PAH can’t convert Phe to Tyr, and Phe builds up
AR
1/10k births
causes mental retardation
treated by diet modification ( low Phe diet) early in life and especially during pregnancy

Question 17

why do pregnant women with PKU need to be careful?

Answer 17

Excess Phe is teratogenic, even if the fetus doesn’t have PKU

Question 18

Non-PKU hyperphenylalaninemia

Answer 18

~10 fold increase in Phe levels
less damaging, may be benign
may not require special diet

Question 19

Variant PKU

Answer 19

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

Question 20

BH4 mutations are an example of

Answer 20

locus heterogenity, when mutations in different genes lead to the same clinical phenotype

Question 21

How is BH4 treated?

Answer 21

oral BH4 and supplementation with neurotransmitters that are lacking

Question 22

Why is a mutation in BH4 more serious?

Answer 22

• may not completely respond to PKU diet
• develop neuro deficits
• cofactor for enzymes needed to make dopamine and serotonin

Question 23

Describe the lysosomal storage diseases

Answer 23

• recessive
• muation in lysosomal hydrolytic enzyme–>failure to degrade
• accumulation of macromolecules
• clinically heterogeneous
• presents with progressive degeneration

Question 24

GM2 Gangliosidoses

Answer 24

Tay-Sachs, Sandhoff’s disease, activator disease

Question 25

Describe Tay Sach’s disease

Answer 25

• AR, rare except with Ashkenazi Jews(carrier frequency 1/27!)
• onset @3-6 motnhs, death by 2-4
• deficiency of hexosaminidase A
• inability to degrade GM2 gangliosides
• no Tx
• cherry red spot on retina, lose control of extremities after being born normal–>death

Question 26

Mucopolysaccaridoses

Answer 26

• group of heterogeneous disorders
• absence of specific enzyme involved in degradation of glycosaminoglycans
• accumulation of macromolecules in the lysosomes
• permanent, progressive damage
• short stature, delay, skeletal abnormalities and joint stiffness, thickened skin, heart, liver or spleen damage

Question 27

How are mucopolysaccarhidoses treated?

Answer 27

bone marrow transplant, enzyme replacement therapy, gene therapy

Question 28

Describe the connective tissue disorders

Answer 28

slightly different as the defects affect structural proteins (fibrillin and collagen)

Question 29

Osteogenesis imperfecta

Answer 29

due to mutations in type 1 collagen with either reduced collagen production or defective collagen;

• brittle bones and skeletal deformities
• reduced collagen production is mildest form
• defective collagen is more severe

Question 30

Ehler Danlos

Answer 30

• error in post-translational modification of collagen
• multiple subtypes
• AD, AR, and X linked recessive
• skin fragility, joint hypermobility, skin hyperextensibility

Question 31

What genes are affected in Ehler Danlos?

Answer 31

COL5A or COL3A

Question 32

Marfan’s Disease

Answer 32

• mutation of the fibrillin gene
• targets: skeleton, eyes, heart, lung
• tall and thin, very long thin fingers–>joint laxity and scoliosis
• lung problems include pneumothorax
• dislocation of lens/myopia, retinal detachment
• mitral valve prolapse, dilation, and dissection of the aorta

Question 33

Karyogram:

Answer 33

an image of the chromosome constitution of an individual. Also, a figure
showing the paired chromosomes from a cell arrayed in a standard sequence.

Question 34

Isodisomy:

Answer 34

2 chromosomes from the same source, i.e., duplication of 1 chromosome

Question 35

Disomy:

Answer 35

the presence of 2 chromosomes; normal state

Question 36

Heterodisomy:

Answer 36

2 different chromosomes

Question 37

Nondisjunction:

Answer 37

failure of chromosomes or chromatids to separate to opposite poles in
cell division. Usually results in one too many or one too few chromosomes in a cell.
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