X-linked

Question 1

Fragile X - Inheritance

Answer 1

X dominant

Question 2

Fragile X - Associated gene

Answer 2

FRM1

Question 3

Fragile X - Mechanism

Answer 3

Trinucleotide repeat disorder 5’ UTR (CGG) (>200 nucleotides)
leads to hypermethylation

anticipation
maternal transmission bias

Question 4

Fragile X - Clinical Presentation

Answer 4

most common cause of inherited developmental delay
dysmorphic features
autistic
social anxiety
hand flapping/biting
aggression

Question 5

Rett - Inheritance

Answer 5

X dominant

Question 6

Rett - Associated gene

Answer 6

MECP2

essential for nerve cell function

Question 7

Hypophosphatemic Rickets - Inheritance

Answer 7

X dominant

Question 8

Hypophosphatemic Rickets - Associated gene

Answer 8

PHEX

inhibits kidney reabsorption of phosphate

Question 9

Lesch-Nyhan - Inheritance

Answer 9

X Recessive

Question 10

Lesch-Nyhan - Associated gene

Answer 10

HPRT1

Question 11

Lesch-Nyhan - Mechanism

Answer 11

Can’t recycle purines - overproduction of uric acid

Question 12

Duchenne Muscular Dystrophy - Inheritance

Answer 12

X Recessive

Question 13

Duchenne Muscular Dystrophy - Associated gene

Answer 13

DMD Dystrophin Gene

Question 14

Duchenne Muscular Dystrophy - Mechanism

Answer 14

large deletion in DMD - frameshift mutation

loss of function - anchors actin filaments to muscle cell wall

Question 15

Duchenne Muscular Dystrophy - Less severe form

Answer 15

Becker Disease
In-frame deletion
Missense

Question 16

Duchenne Muscular Dystrophy - Clinical presentation

Answer 16

progressive muscle weakness (proximal –> distal)
calf hypertrophy (adipose)
dilated cardiomyopathy
increased creatine kinase levels (muscle damage)
onset ~2 years
death in 30s

Question 17

Hemophilia A - Inheritance

Answer 17

X Recessive

Question 18

Hemophilia A - Associated gene

Answer 18

F8

Question 19

Hemophilia A - Mechanism

Answer 19

Intragenic inversion of F8

Factor VIII deficiencey

Question 20

Hemophilia A - Clinical presentation

Answer 20

Blood won’t clot
Can supplement
improves with puberty

Question 21

Fabry disease - Inheritance

Answer 21

X Recessive

Question 22

Fabry Disease - Associated protein

Answer 22

Gene coding for alpha-galactosidase enzyme

Question 23

Fabry Disease - Mechanism

Answer 23

Misfolding of alpha-galactosidase enzyme
Lysosomal storage disease
alpha-galactosidase doesn’t break down glycosphingolipids
Lipids accumulate in lysosomes leading to microvascular damage

Question 24

Fabry Disease - Clinical presentation

Answer 24

Neurological pain in childhood
Decreased sweating
Progressive renal failure
risk of heart attack, stroke

Question 25

Fabry Disease - Therapy

Answer 25

Chaperone based

Enzyme replacement therapy

Question 26

Androgen Insensitivity - Inheritance

Answer 26

X Recessive