Intro to Medical Genetics - RR Flashcards
What are the two subspecialties of genetics in medicine?
- Human genetics- the study of human heredity specifically
2. Medical genetics- study of human genetic variation of medical significance
There are 5 different subspecialties of medical genetics. What are they and which ones are considered clinical/laboratory?
Diagnostic genetics (clinical) Genetic counseling (clinical) Molecular genetics (lab) Biochem genetics (lab) Cytogenetics (lab)
What is the definition of a mutation? Are all mutations deleterious?
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
What is the difference between an inherited gene complement and an acquired gene complement?
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
What is the definition of a syndrome?
A set of characteristics that occur together and are assumed to have a common basis. These characteristics will vary from individual to individial
Alcaptonuria, cystonuria, pentosouria, and albinism are caused by inborn errors of metabolism that are autosomal dominant or autosomal recessive?
Autosomal recessive
Alcaptonuria is due to an accumulation of what substrate? How is it detected?
Accumulation of homogentisic acid (defect in the enzyme homogentisic acid oxidase)
Detected by a change in urine color
Normally tyrosine is converted into melanin to produce pigment. A defect in which enzyme results in albinism?
Tyrosine oxidase
What characterizes inborn errors of metabolism? (both in inheritance and in manifestation)
Caused by a single enzyme defect
Autosomal recessive
Manifests: Poor growth, mental retardation, problems with general metabolism, neuro problems
What are some features that may indicate an inborn error of metabolism?
Patient shows common characteristics, there’s a family history positive for other affected individuals, and unexplained infant deaths
What happens when there’s a defect in phenylalanine hydroxylase? What is there an accumulation of? What is there a deficit of?
phenylalanine builds up
deficient in tyrosine
How does hyperphenylalaninemia manifest? How is it treated?
Mental retardation (neuro problems) Treated with a diet low in phenylalanine
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?
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
What is non-PKU hyperphenylalaninemia? Do they need a PKU diet? (according to Stein’s definition)
Have a deficit of phenylalanine hydroxylase but not a complete loss
This is less severe and may not require a PKU diet
What is variant PKU? Do they need a PKU diet?
Somewhere between non-PKU and PKU
-requires a PKU diet but not as restrictive as with full on PKU
What is the definition of locus heterogeneity in terms of disease?
Mutations in different genes that lead to the same phenotype
A deficit in which cofactor is an example of locus heterogeneity with regard to PKU?
BH4
A deficiency of BH4 causes the accumulation of numerous substrates and a deficiency of different products. What are these substrates and products?
Excess of phenylalanine and tryptophan
Deficient in serotonin and dopamine
A patient presents with high levels of phenylalanine. You find that this is from deficiency in BH4. How do you treat them?
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
Progressive autosomal recessive disorders that are due to a mutation in a hydrolytic enzyme are known as what general disease?
Lysosomal storage diseases
What is an example of a GM2 gangliosidose disease? What can not be broken down? What are the characteristics of this disease?
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
What can not be broken down in mucopolysaccharidoses?
Mucopolysaccharides and GAGs
-note that each mucopolysaccharide has it’s own specific enzyme
What are common characteristics seen in those with mucopolysaccharidoses?
Short stature, delay, joint thickness, thick skin, heart/liver/spleen damage
These are permanent and progress over time
How can mucopolysaccharidoses be treated?
Bone marrow transplant, enzyme replacement, gene therapy
A mutation in what structural protein results in osteogenesis imperfecta? How is this mutation inherited?
Collagen Type I
Autosomal dominant
A mutation in what structural protein results in Ehlers-Danlos syndrome? How is this disease characterized?
Mutation in post-translational modification of collagen
Character: hypermobility of joints, fragile skin, increased elasticity
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?
Child abuse
Ehlers Danlos- because have skin fragility with poor wound healing
A mutation in what structural protein results in Marfan syndrome? What organs are affected? How is this syndrome characterized?
Mutation in fibrillin
Affects skeleton, eyes, and heart– worry about aortic dissection/mitral valve prolapse
Character: tall, thin, long fingers
