MCP 1

Question 1

Define Human genetics

Answer 1

the study of heredity in man and WOMAN

Question 2

Define medical genetics

Answer 2

the study of human genetic variation of medical significance

Question 3

Subunits of medical genetics

Answer 3

1. clinical genetics-diagnosis
2. genetic counseling-information
3. molecular genetics - lab
4. biochemical genetics - lab
5. cytogenetics - lab

Question 4

Define mutation

Answer 4

-a 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- blue eyes
positive- sickle cell trait
negative- sickle cell disease, cancer

Question 5

Identify the two patterns of inheritance

Answer 5

dominant vs. recessive

autosomal vs. X-linked

Question 6

define inherited disease

Answer 6

inherited gene complement-mutations may be transmitted from one or both parents
-typically called the constitutional genome

Question 7

define acquired disease

Answer 7

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

Question 8

Syndrome

Answer 8

a set of characteristics which occur together and are assumed to have a common basis

• not all character occur in all affected individuals (example VCFS)
• range of variability within a population

Question 9

define biochemical genetics

Answer 9

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

Question 10

Define in-born errors of metabolism

Answer 10

genetically determined biochemical disorder in which a specific enzyme defect produces a metabolic block leading to either..
-accumulation of substrate
or
-deficiency of products

Question 11

Alkaptonuria

Answer 11

deficiency in homogenstic acid oxidase -> leading to the accumulation of homogentisic acid in the blood; damage to cartilage, heart kidney -> arthritis in 30s

Question 12

Albinism

Answer 12

deficiency in tyrosine oxidase -> lack of melanin production and lack of pigmentation -> can be either partial or complete

Question 13

salvage pathways

Answer 13

can spare the over accumulation of potentially toxic substances in cells - and make other by products with the accumulated intermediate

Question 14

List some characteristics of in-born errors of metabolism

Answer 14

• single enzyme defect

- recessive

Question 15

General clinical features of in-born errors of metabolism

Answer 15

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

Question 16

Hyperphenylalaninemias

Answer 16

PKU->defect in phenylalanine hydroxlase
abnormal PKU -> defects in tetrahydrobiopterin metabolism
- the pheylalanine builds up and a small amount is converted to pheylpyruvic acid which can be detected in urine

Question 17

PKU

Answer 17

1/10,000 live births
autosomal recessive
treat by modifying diet -> early in life and in pregnancy

Question 18

non-PKU hyperpheylalaninemia

Answer 18

• 10 fold increase in PHE levels
• less damaging
• may not require a special diet

Question 19

Variant PKU

Answer 19

• between full PKU and non-PKU hyperphenylalaninemia

- requires a diet, but not as restrictive as PKU pateints

Question 20

Lysosomal storage diseases

Answer 20

• autosomal recessive
• mutation of lysosomal hydrolytic enzymes leads to failure of degeneration and the accumulation of macromolecules in lysosomes
• over 50 known deficiencies
• clinically heterogeneous
• common presentation; progressive degeneration

Question 21

Tay Sachs Disease

Answer 21

• autosomal recessive
• rare except in Ashkenazi jews (carrier frequency 1/27)
• onset 3-6 months
• death by 2-4 years of age
• inability to degrade GM2 ganglioside
• deficiency of hexosaminidase A
• inability to degrade gangliosides GM2
• no known treatment
• clinically significant finding is the cherry red spot in the eye (retina)

Question 22

Define Mucopolysaccharidoses

Answer 22

• group of heterogeneous disorders
• absence of specific enzyme involved in degradation of glycosaminoglycans (degradation requires stepwise removal of subunits so if one enzyme is missing along the chain the chain will not be degraded and this product will accumulate)
• accumulation of macromolecules in the lysosomes

Question 23

Clinical features of Mucopolysaccharidoses

Answer 23

• permanent, progressive damage

- short stature, delay, skeletal abnormalities and joint stiffness, thickened skin, heart liver or spleen damage

Question 24

Treatment for Mucopolysaccharidoses

Answer 24

-bone marrow transplant
enzyme replacement therapy
gene therapy

Question 25

Osteogenesis imperfecta

Answer 25

• connective tissue disorder
• due to a defect in type 1 collagen
• autosomal dominant
• four different classes range from mild-> lethal
  a) type II is perinatal lethal
  b) type IV is mild to moderate bone deformity and fracturing
  c) Type III is more severe -intermediate between II and IV

Question 26

Ehler-Danlos Syndrome

Answer 26

-error in post-translational modification of collagen
-multiple subtypes
-autosomal dominant, autosomal recessive and X linked recessive
characters: joint hypermobility, skin fragility and hyperexntesibiltiy
most common mutation is in COL5A or COL3A genes

Question 27

Marfan Syndrome

Answer 27

• a connective tissue disorder
• related to a mutation if fibrillin gene
• primary defects seen in skeleton, eyes (lens displacement), lung (pneumothorax) and heart (dissection of aorta)
• patients have very long, thin fingers, with joint laxity and scoliosis
• no known treatment but being aware of diagnosis is key to manage symptoms and limit stressful activities