Introduction to Medical Genetics

Question 1

medical genetics

Answer 1

the study of human genetic variation of medical significance

-vs human-study of heredity in man

Question 2

subunits of medical genetics

Answer 2

• clinical genetics-diagnosis
• genetic counseling- info
• molecular genetics, biochemical, cytogenetics-lab

Question 3

mutation

Answer 3

• permanent, heritable change in the sequence of genomic DNA
• can occur at either the molecular or cytogenetic level
• may give rise to new alleles
• important mechanism of population variation
• neutral mutation-blue eyes
• pos-sickle cell trait
• neg-sickle cell disease

Question 4

patterns of inheritance

Answer 4

• dominant vs recessive

- autosomal vs x linked

Question 5

inherited gene complement

Answer 5

• mutations may be transmitted from one or both parents

- typically called the constitutional genome

Question 6

acquired gene complement

Answer 6

-subset of cells in an individual that arose by clonal propagation from a single mutation in one cell

Question 7

syndrome

Answer 7

• set of characteristics which occur together and are assumed to have a common basis
• not all characters occur in all affected individuals
• range of variability within a population
• VCFS-250 features, no single person has all of them

Question 8

biochemical genetics

Answer 8

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

Question 9

inborn errors of met

Answer 9

• genetically determined biochemical disorder in which a specific enzyme defect produces a metabolic block
• accumulation of substrate
• deficiency of products
• first reported in 1908-alcaptonuria, cystonuria, pentosuria, albinism

Question 10

alkaptonuria

Answer 10

-accumulation of homogentisic acid in the blood, damage to cartilage, heart, kidney

Question 11

pathways

Answer 11

• depending on what enzyme is gone, substrates will accumulate
• different color kitties-tyrosine oxidase leads to white kitty

Question 12

enzyme defects

Answer 12

• secondary pathways may show increases in activity if primary can’t work
• salvage pathways

Question 13

shared enzymes

Answer 13

-both products decrease and both precursors accumulate

Question 14

inborn errors 2

Answer 14

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

Question 15

general clinical features of metabolic disorders

Answer 15

• poor growth
• mental retardation
• problems in general metabolism
• neurological problems
• patient evaluation- clinical picture- onset of MR over time
• family history- other affected siblings, unexplained infant deaths

Question 16

biochemical genetic diseases

Answer 16

• aminoacidopathies
• organic acidemias
• FA oxidation disorders
• urea cycle disorders
• carb metabolism disorders
• glycogen storage disease
• lysosomal storage diseases

Question 17

hyperphenylalaninemias

Answer 17

• PKU, variant PKU
• defects in BH4 metabolism
• phenylalanine hydroxylase

Question 18

PKU

Answer 18

• phenylalanine hydroxylase to tyrosine
• build up and phenylpyruvic acid
• AR
• 1/ 10,000 live births
• treat by diet modification- early in life and in pregnancy
• low Phe diet

Question 19

variant PKU and non PKU-hyperphenylalaninemia

Answer 19

• non PKU- 10 fold increase in Phe levels, less damaging, may be benign, may not require diet
• variant PKU- b/n extremes- requires a diet but not as restrictive
• clinical heterogeneity-different phenotypes from mutation of a single gene

Question 20

BH4

Answer 20

• used with phenylalanine hydroxylase
• if deficient, can have PKU
• defect of BH4 metabolism, not the PAH
• locus heterogeneity- mutations in different genes leading to same disease, dont completely respond to diet
• also cofactor for other reactions-deficit of dopamine and serotonin
• give BH4 and nts

Question 21

lysosomal storage diseases

Answer 21

• recessive
• mutation of a lysosomal hydrolytic enzyme leads to failure of degradation and the accumulation of macromolecules in lysosomes
• over 50 known
• clinically heterogeneous
• common presentation: progressive degeneration

Question 22

lysosomal storage diseases 2

Answer 22

• cystinosis
• fabry
• gaucher
• i cell disease
• krabbe
• metachromatic leukodystrophy
• mucopolysaccharidosis
• niemann pick
• pompe
• sulfatase def
• tay sachs

Question 23

GM2 gangliosidoses

Answer 23

• three different genes produce 3 different proteins that function together
• mutation in any one can result in abnormality

Question 24

tay sachs

Answer 24

• AR
• rare except for ashkenazi jews
• onset 3-6 months, death 2-4 years
• deficiency of hexosaminidase A
• inability to degrade GM2 ganglioside
• no known trt
• carrier rate 1/27
• accumulation in brain
• cherry red macula

Question 25

mucopolysaccharideoses

Answer 25

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

Question 26

hunter

Answer 26

-iduronate sulfatase (enzyme) -build up of dermatan sulfate and heparan sulfate X linked recessive

Question 27

hurler

Answer 27

- a-L-iduronidase | - dermatan and heparan sulfate

Question 28

Scheie

Answer 28

- a-L-iduronidase | - dermatan and heparan sulfate

Question 29

sanfilippo

Answer 29

- 4 enzymes | - heparan sulfate

Question 30

morquio a

Answer 30

- gal-6-sulfatase | - keratan sulfate

Question 31

morquio b

Answer 31

- b galactosidase | - keratan sulfate

Question 32

maroteaux-lamy

Answer 32

- arysulfatase B | - dermatan sulfate

Question 33

sly

Answer 33

- b glucuronidase | - dermatan and heparan sulfate

Question 34

treatment for mucopolysaccharidoses

Answer 34

- bone marrow transplantation - enzyme replacement therapy - gene therapy

Question 35

CT disorders: collagen

Answer 35

- procollagen/collagen - collagen fibril - mineralization in bone

Question 36

OI

Answer 36

- mutations in type 1 collagen with either reduced production or defective collagen - 4 classes - AD - brittle bones and skeletal deformities - reduced production is mildest class, produced in half normal quantity - type II is perinatal lethal - type IV is mild to moderate bone deformity and fracturing, class III is intermediate

Question 37

ehler-danlos

Answer 37

- error in post translational modification of collagen - multiple subtypes - AD, AR, x linked recessive - skin fragility - joint hypermobility - skin hyperextensibility - COL5A or COL3A - shunned/freaks/circus

Question 38

Marfan

Answer 38

- CT- fibrillin gene - skeleton, eyes, heart - tall and thin with long fingers - joint laxity and scoliosis - lung-pneumothorax - dislocation of lens, cataracts, glaucoma, retinal detachment - mitral valve prolapse, dilatation and dissection of aorta (athletes)