X-linked

Question 1

Mechanism of X chromosome inactivation -

Answer 1

XIST gene located on the X chromosome

expressed only from the inactive X

required for X inactivation

Question 2

Hypophasphatemic rickets
inheritance
incidence

Answer 2

X-linked dominant

1/20,000

Question 3

Hypophosphatemic rickets

clinical

Answer 3

low phosphate in blood
short stature
bone deformity

Question 4

Hypophosphatemic rickets

mutation?

Answer 4

PHEX
Regulates fibroblast growth factor
Inhibits kidneys ability to reabsorb phosphate into the blood stream

Question 5

Fragile X
inheritance
mutation?

Answer 5

X linked dominant

FMR1

Question 6

Fragile X

mutation issue?

Answer 6

trinculeotide repeat

CGG

Question 7

Fragile X
incidence
m and f

Answer 7

m
1/2500-4000
f
1/7000-8000

Question 8

What is the most common caused of inherited developmental delay?

Answer 8

fragile x

Question 9

Since fragile x is a trinucleotide repeat, what do we see?

Answer 9

anticipation

Question 10

fragile x

parental bias

Answer 10

mom

Question 11

fragile x

clinical

Answer 11

intellectual
dysmophic: large ears, long face, macroorchidism
autistic
anxiety 
hand flapping biting 
aggression

Question 12

fragile x premutation FMR1 associated conditions?

Answer 12

Fragile x associated tremor ataxia FXTAS - white matter lesion on MRI / intention tremor / gait ataxia

FMR1 -related primary ovarian insufficiency - menopause

Question 13

fragile x CGG thresholds

Answer 13

6-45 normal
46-55 grey
56-200 Premutation (FXTAS/POI)
>200 full mutation

Question 14

Rett Syndrome
inheritance?
incidence
new mutation?

Answer 14

X linked dominant
1/10,000
95%

Question 15

Rett

clinical?

Answer 15

loss of normal coordination
acquired microcephaly
loss of communication
failure to thrive
seizures
abnormal hand movement

Question 16

Rett

mutation?

Answer 16

MECP2
MethyL CpG binding protein
Essential for normal function of nerve cells

Question 17

Lesch Nyhan
inheritance
incidence

Answer 17

X linked recessive

1/380,000

Question 18

Lesch Nyhan

Clinical?

Answer 18

cerebral palsy
cognitive/behavior
overproduction uric acid
self injury

Question 19

Lesch Nyhan mutation?

Answer 19

HPRT1
Hypoxanthine phosphoribosyltransferase 1
Recycling of purines

Question 20

Dytrophinopathies
inheritance
what are they
3 examples

Answer 20

x-linked recessive
spectrum of muscle diseases from mild to severe

Becker MD
Duchenne MD
DMD associated dilated cardiomyopathy

Question 21

Dystrophinopathies
Mutation?
Loci?

Answer 21

DMD
Xp21-21.1
dystrophin

Question 22

What is the largest human gene?

Answer 22

dystrophin

Question 23

Duchenne

Clinical

Answer 23

progressive muscle weakness from proximal to distal
calf hypertrophy
dilated cardiomyopathy
CK level 10x normal
onset before 5
wheelchair bound before 13
death in 30s 
absence of dystrophin

Question 24

Becker

Clinical

Answer 24

Progressive muscle weakness proximal > distal
dilated cardiomyopathy
CK levels 5x normal
later onset
wheelchair bound after 16
death in 40s
abnormal quality dystrophin

Question 25

DMD associated DCM | Clinical

Answer 25

dilated cardiomyopathy presenting between 20-40 early death no skeletal muscle involvement no dystrophin in myocardium

Question 26

Hemophilia A inheritance incidence carrier females affected?

Answer 26

x linked recessive 1/4000 male births 10% carrier females affected

Question 27

Hemophilia A | clinical

Answer 27

blood disorder where blood fails to clot due to deficient factor VIII Spontaneous bleeds into joints, muscles, or intracranial excessive bruising prolonged bleeding delayed wound healing royal family

Question 28

Hemophilia A | gene mutated?

Answer 28

F8 Xq28 Deficient factor VIII

Question 29

50% hemophila A is due to?

Answer 29

22A inversion

Question 30

``` Mitochondrial DNA #genes ```

Answer 30

37

Question 31

Characteristics of mtDNA (4)

Answer 31

maternal inheritance replicative segregation homoplasmy/heteroplasmy threshold effect

Question 32

mtDNA | Replicative segregation

Answer 32

At cell division the multiple copies of mtDNA replicate and sort randomly among newly synthesized mitochondria this could be normal or mutated DNA

Question 33

Heteroplasmy

Answer 33

Cells have both mutant and normal mitochondria / threshold for if phenotypic consequence

Question 34

mitochondrial disease tends to affect tissues that?

Answer 34

``` Rely on oxidative phosphorylation brain retina skeletal muscle heart ```

Question 35

mitochondrial diseases (4)

Answer 35

Kearns-Sayre syndrome MELAS MERRF Leber Hereditary Optic Neuropathy

Question 36

Kearns Sayre Syndrome | incidence

Answer 36

mtDNA - large deleation (usually removes 12 genes) 1-3/100,000 Most commonly caused by somatic mutation

Question 37

Kearns Sayre | clinical

Answer 37

triad - pigmentary retinopathy - progessive external ophthalmoplegia - onset before 20 cardiac conduction defects ataxia deafness kidney problems

Question 38

MELAS Mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes inheritance incidence new mutation?

Answer 38

mitochondrial 1/300,000 low new mutation

Question 39

MELAS | clinical

Answer 39

``` 2-10y/o muscle weakness seizures repetetive stroke like episodes elevated lactic acidosis ```

Question 40

MELAS Mutations?

Answer 40

Mitochondrial genes | MT - ND1/ND5/TH/TL1 (80%) /TV)

Question 41

MERRF | Myocloinic epilepsy with ragged red fibers

Answer 41

mt 1/400,000 low new mutation

Question 42

MERRF | CLINICAL

Answer 42

``` muscle symptoms seizures ataxia dementia ragged red fibers ```

Question 43

MERRF | Mutation?

Answer 43

mitochondrial genes | MT-TK

Question 44

Leber Hereditary Optic Neuropathy

Answer 44

mt | 1/30-50,000 europeans

Question 45

Leber Hereditary Optic Neuropathy

Answer 45

bilateral subacute vision failure | occurs during young adulthood

Question 46

Leber Hereditary Optic Neuropathy | Mutation?

Answer 46

mt DNA | point mutations