Genetics

Question 1

3 Primary Types of Mutations

Answer 1

genome mutation
chromosomal mutation
gene variant

Question 2

genome mutation

Answer 2

loss or gain of an entire chromosome

Question 3

chromosomal mutation

Answer 3

alteration of a segment of chromosome

Question 4

gene varient

Answer 4

partial or complete deletion of a gene

Question 5

how many chromosomes in a typical human

Answer 5

46, 23 pairs

Question 6

how many autosomal chromosomes pairs

Answer 6

22 pairs

Question 7

hereditary or familial

Answer 7

condition derived from parents due to a genetic mutation

Question 8

congenital

Answer 8

condition present at birth; may be hereditary or derived from action or exposure during pregnancy or birth

Question 9

autosomal dominant

Answer 9

the gene in question is located on one of the 44 numbered, or non-sex, chromosomes

Question 10

dominant

Answer 10

a single copy of the mutated gene is enough to cause phenotypic expression

Question 11

clinical manifestations of familial hypercholesterolemia

Answer 11

• Elevated blood cholesterol levels
• Atherosclerosis resulting in cardiovascular disease
• Death before the age of 30 due to uncontrolled CVD

Question 12

hypercholesterolemia is a mutation of

Answer 12

LDL
receptor mutation that results in impaired uptake of cholesterol into cells

Question 13

clinical manifestation of marfan syndrome

Answer 13

Skeletal: Long arms, legs, and fingers
Eye: Bilateral dislocation of the lens
Cardiovascular: Aortic root dilation, leading to aortic insufficiency, Myxomatous mitral valve, Ascending thoracic aortic aneurysms, Aortic dissection

Question 14

T or F osteogenesis imperfecta is heterogeneous

Answer 14

T

Question 15

osteogenesis imperfecta

Answer 15

Pleiotropic - one gene influences >2 phenotypic traits
80% autosomal dominant
20% autosomal recessive
90% of cases are cause by a mutation of collagene coding gene

Question 16

pathophysiology of osteogenesis imperfecta

Answer 16

Disease of the Type 1 Collagen: major extracellular protein in the body
Dermis
Connective Tissue of the organs, GI, and vascular system
Bones

Question 16

osteogenesis imperfecta

Answer 16

Brittle Bone disease
Significant phenotypic heterogeneity between subtypes and within subtypes
X-rays show mild osteopenia

Question 17

type 1 OI

Answer 17

mildest form of OI
fracture
blue sclera
short stature
75% autosomal dominant inheritance - 25% new mutations

Question 18

type 2 OI: perinatal lethal

Answer 18

• Most severe form of brittle bone disease
  Can be life-threatening presents at or before birth with multiple fractures, bony deformities, significant fragility of nonbony connective tissue, blue sclera, short limbs, small chest, and soft skull
  Inadequate and poor quality collagen production
  Hallmark characteristic  Hips in external rotation & abduction  ‘frog-leg’ position

Typically results in death in infancy

Radiologic findings isolated “islands” of mineralization in the skull and beaded appearance in the ribs
Nearly all cases are a new dominant mutation no family history

Question 19

type 3 OI: severe- progressive deforming

Answer 19

Presents at birth or infancy with progressive bony deformities, multiple fractures, and blue sclera

• Most individuals will require multiple corrective surgeries and lose the ability to walk by early adulthood

Nearly all cases due to dominant mutation – rarely inherited recessively

Question 20

type 4 OI: moderately severe

Answer 20

• Moderate to severe growth retardation distinguishing factor from Type 1
• Bony deformities, blue sclera, very short ‘long” bones
• Postnatal fractures ranging from severity of Type 1 to Type 3
• Child may fracture later  when learning to walk

Severity of symptoms: Type 1 < Type 4< Type 3 < Type 2

Question 21

cycstic fibrosis clinical
manifestations

Answer 21

• Fibrosis of pancreas
  -Recurrent pulmonary infections  pneumonia
  -Chronic bronchitis, bronchiectasis
  -Meconium ileus
  -Biliary cirrhosis, leading to impaired absorption of the fat-soluble vitamins A, D, E, and K
  -Infertility in males secondary to absence of vas deferens
  -Thick and sticky mucus  secondary to absence of chloride on cell surface

Question 22

x linked recessive

Answer 22

Refers to genetic conditions associated with mutations in genes on an X chromosome

Question 23

x linked recessive: Muscular dystrophy clinical manifestation

Answer 23

• Weakness of pelvis first  delayed ability to walk
• Pseudohypertrophy  enlargement of calf muscles due to replacement with fat
• Gower maneuver  use of hands to rise to a standing position
• Muscle atrophy and weakness progress relentlessly wheelchair dependent by the second decade
• In most cases, death due to respiratory insufficiency and cardiac failure

Question 24

x linked recessive muscular dystrophy

Answer 24

• profound male predominance; female carriers of the disease are typically asymptomatic
• Clinical course: Disease manifests by the age of 5 years associated muscular weakness leads to immobility by the early teens  usually death by the 20s or 30s. Cardiomyopathy and non-progressive cognitive abnormalities are also fairly common

Question 25

chromosomal inheritance pattern

Answer 25

Mutation of a large segment or entire chromosome

Question 26

down syndrome

Answer 26

extra copy of chromosome 21 in each cell - trisomy 21
1 in 700 newborns

Question 27

down syndrome clinical manifestations

Answer 27

Intelectual disability
Characteristic facial features
Hypotonia
Protruding tongue
Congenital heart disease

Question 28

trisomy 18 clinical manifestation

Answer 28

Heart/organ defects
Small and abnormally shaped head, small jaw and mouth
Clenched fists with overlapping fingers

Question 29

ehlers-danlos-syndrome

Answer 29

Hereditary collagen disorder characterized by articular hypermobility, dermal hyperelasticity, and widespread tissue fragility
- mutations in at least 20 genes

Question 30

EDS clinical manifestation

Answer 30

Hyperextensible skin
Fragile tissue
Poor wound healing
Joint hypermobility
Increased propensity for joint subluxation
Muscle weakness
Delayed motor development
Fatigue
Gait defects
Chronic pain

Question 31

cystic fibrosis mutation

Answer 31

Cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7

Question 32

cystic fibrosis epidemiology

Answer 32

: 1 in 3500 live births; whites predominantly

Question 33

duchenne muscular dystrophy epidemiology

Answer 33

1 in 3000 infants; profound male predominance; female carriers of the disease are typically asymptomatic
Clinical course: Disease manifests by the age of 5 years associated muscular weakness leads to immobility by the early teens  usually death by the 20s or 30s. Cardiomyopathy and non-progressive cognitive abnormalities are also fairly common

Question 34

trisomy 18 facts

Answer 34

Individuals with trisomy 18 often have slow growth before birth  low birth weight
Due to the presence of several life-threatening medical problems, many individuals with trisomy 18 die before birth or within their first month.
Five to 10 percent of children with this condition live past their first year, and these children often have severe intellectual disability.
Epidemiology: 1 in 5,000 live births

Question 35

genetic conditions with mixed inheritance patterns

Answer 35

Depending on the condition and the gene involved, the inheritance pattern can be autosomal dominant, autosomal recessive, or X-linked recessive

Ehlers-Danlos Syndrome

Question 36

PT implications of EDS

Answer 36

Joint stability  low resistance, high repetition
Assistive device for loading relief
Bracing to promote joint stability decrease incidence of subluxing
Pain management