Intro to Medical Genetics - RR

Question 1

What are the two subspecialties of genetics in medicine?

Answer 1

1. Human genetics- the study of human heredity specifically

2. Medical genetics- study of human genetic variation of medical significance

Question 2

There are 5 different subspecialties of medical genetics. What are they and which ones are considered clinical/laboratory?

Answer 2

Diagnostic genetics (clinical)
Genetic counseling (clinical)
Molecular genetics (lab)
Biochem genetics (lab)
Cytogenetics (lab)

Question 3

What is the definition of a mutation? Are all mutations deleterious?

Answer 3

A permanent, heritable change in the sequence of genomic DNA
Not all mutations are harmful- there can be negative, positive, or neutral mutations
Negative: cancer, sickle cell disease
Positive: sickle cell trait (heterozygous)
Neutral: blue eyes

Question 4

What is the difference between an inherited gene complement and an acquired gene complement?

Answer 4

Inherited gene complement: inherited mutation from one or both parents that are found in the early embryo and consequently found in all cells; also called constitutional genome
Acquired gene complement: a subset of cells that arises from a spontaneous mutation in one cell that then proliferates, propagating this mutation

Question 5

What is the definition of a syndrome?

Answer 5

A set of characteristics that occur together and are assumed to have a common basis. These characteristics will vary from individual to individial

Question 6

Alcaptonuria, cystonuria, pentosouria, and albinism are caused by inborn errors of metabolism that are autosomal dominant or autosomal recessive?

Answer 6

Autosomal recessive

Question 7

Alcaptonuria is due to an accumulation of what substrate? How is it detected?

Answer 7

Accumulation of homogentisic acid (defect in the enzyme homogentisic acid oxidase)
Detected by a change in urine color

Question 8

Normally tyrosine is converted into melanin to produce pigment. A defect in which enzyme results in albinism?

Answer 8

Tyrosine oxidase

Question 9

What characterizes inborn errors of metabolism? (both in inheritance and in manifestation)

Answer 9

Caused by a single enzyme defect
Autosomal recessive
Manifests: Poor growth, mental retardation, problems with general metabolism, neuro problems

Question 10

What are some features that may indicate an inborn error of metabolism?

Answer 10

Patient shows common characteristics, there’s a family history positive for other affected individuals, and unexplained infant deaths

Question 11

What happens when there’s a defect in phenylalanine hydroxylase? What is there an accumulation of? What is there a deficit of?

Answer 11

phenylalanine builds up

deficient in tyrosine

Question 12

How does hyperphenylalaninemia manifest? How is it treated?

Answer 12

Mental retardation (neuro problems)
Treated with a diet low in phenylalanine

Question 13

A pregnant woman who was diagnosed with PKU as a child, has a fetus that does not have PKU. Does she need to be on a PKU diet?

Answer 13

Yes- the excess phenylalanine can cross the placenta and even though the fetus doesn’t have PKU the excess can affect development within the fetus

Question 14

What is non-PKU hyperphenylalaninemia? Do they need a PKU diet? (according to Stein’s definition)

Answer 14

Have a deficit of phenylalanine hydroxylase but not a complete loss
This is less severe and may not require a PKU diet

Question 15

What is variant PKU? Do they need a PKU diet?

Answer 15

Somewhere between non-PKU and PKU

-requires a PKU diet but not as restrictive as with full on PKU

Question 16

What is the definition of locus heterogeneity in terms of disease?

Answer 16

Mutations in different genes that lead to the same phenotype

Question 17

A deficit in which cofactor is an example of locus heterogeneity with regard to PKU?

Answer 17

BH4

Question 18

A deficiency of BH4 causes the accumulation of numerous substrates and a deficiency of different products. What are these substrates and products?

Answer 18

Excess of phenylalanine and tryptophan

Deficient in serotonin and dopamine

Question 19

A patient presents with high levels of phenylalanine. You find that this is from deficiency in BH4. How do you treat them?

Answer 19

Supplement with BH4, L-Dopa, and 5-OH
A patient deficient in BH4 won’t respond to a PKU diet because they’re still deficient in serotonin and dopamine so have to provide their intermediates

Question 20

Progressive autosomal recessive disorders that are due to a mutation in a hydrolytic enzyme are known as what general disease?

Answer 20

Lysosomal storage diseases

Question 21

What is an example of a GM2 gangliosidose disease? What can not be broken down? What are the characteristics of this disease?

Answer 21

Tay Sach’s- deficiency of hexosaminidase A
Can’t break down gangliosides- to breakdown need three functional proteins and if missing one then get the disease
Characteristics: appear normal at birth and then see symptoms at 3-6 months which progresses to death by 2-4 years. Progressive loss of neuro and initially see a cherry red spot in retina

Question 22

What can not be broken down in mucopolysaccharidoses?

Answer 22

Mucopolysaccharides and GAGs

-note that each mucopolysaccharide has it’s own specific enzyme

Question 23

What are common characteristics seen in those with mucopolysaccharidoses?

Answer 23

Short stature, delay, joint thickness, thick skin, heart/liver/spleen damage
These are permanent and progress over time

Question 24

How can mucopolysaccharidoses be treated?

Answer 24

Bone marrow transplant, enzyme replacement, gene therapy

Question 25

A mutation in what structural protein results in osteogenesis imperfecta? How is this mutation inherited?

Answer 25

Collagen Type I

Autosomal dominant

Question 26

A mutation in what structural protein results in Ehlers-Danlos syndrome? How is this disease characterized?

Answer 26

Mutation in post-translational modification of collagen

Character: hypermobility of joints, fragile skin, increased elasticity

Question 27

A pediatric patient presents in the ER with wounds that do not seem to heal. This is not the first time he has been in the ER for these wounds. What is on the differential?

Answer 27

Child abuse

Ehlers Danlos- because have skin fragility with poor wound healing

Question 28

A mutation in what structural protein results in Marfan syndrome? What organs are affected? How is this syndrome characterized?

Answer 28

Mutation in fibrillin
Affects skeleton, eyes, and heart– worry about aortic dissection/mitral valve prolapse
Character: tall, thin, long fingers