X linked and mitochondrial inheritance

Question 1

X chromosome inactivation occurs when?

Answer 1

1st week of embryogenesis

Question 2

Nonrandom vs skewed x chromosome inactivation

Answer 2

Nonrandom- when structurally abnormal x chromosome present, more of normal xs are turned on usually
Skewed- observed when female shows signs of x linked recessive condition

Question 3

X linked dominant conditions (4)

Answer 3

Hypophosphatemic Rickets
Fragile X syndrome
Charcot Marie Tooth
Rett Syndrome

Question 4

Clinical manifestation of hypophosphatemic rickets (3)

Answer 4

Hypophosphatemia
short stature
bone deformity

Question 5

Mutation leading to hypophosphatemic rickets occurs on the ____ gene which regulates _____. This inhibits ______

Answer 5

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

Question 6

Fragile X syndrome gene

Answer 6

FMR1

Question 7

Fragile X syndrome exhibits ______ and ________.

Answer 7

Anticipation

Maternal transmission bias

Question 8

Clinical manifestations of Fragile X (6)

Answer 8

intellectual disabilities
large ears, long face, macroorchidism
autistic behavior
social anxiety
hand flapping/biting
agression

Question 9

Other conditions associated with FMR1

Answer 9

Fragile X Associated Tremor Ataxia (FXTAS)

FMR1- related primary ovarian insufficiency

Question 10

CGG repeats fragile X: grey zone, premutation, and full mutation

Answer 10

46-65: Grey
56-200: Premutation
>200: Full mutation

Question 11

Mutation rate of Rett syndrome

Answer 11

95%

Question 12

Clinical Manifestations of Rett syndrome (6)

Answer 12

Loss of normal movement and coordination 
Acquired microcephaly
Loss of communication skills
Failure to thrive
Seizures
Abnormal hand movements

Question 13

Rett syndrome gene mutation

Answer 13

MECP2

Question 14

MECP2 gene (Rett) encodes for what protein?

Answer 14

Methyl CpG binding protein

Essential for the normal function of nerve cells

Question 15

X-linked Recessive Disorders (4)

Answer 15

Lesch-Nyhan Syndrome
Hemophilia A
Fabry’s disease
Dystrophonpathies

Question 16

Clinical Manifestations of Lesch-Nyhan (4)

Answer 16

Cerebral palsy
Cognitive and behavioral disturbances
Overproduction of uric acid
Self injury

Question 17

Gene mutation Lesch Nyhan

Answer 17

HPRT1
Hypoxthine phosphoribosyltransferase
recycling of purines

Question 18

Gene mutation for Duchenne and Becker Muscular dystrophies

Answer 18

DMD

encoding for dystrophin

Question 19

Location of DMD on chromosome

Answer 19

Xp21-21.1

Question 20

Clinical Manifestations of Duchenne (8)

Answer 20

Progressive muscular weakness proximal > distal
Calf hypertrophy
Dilated cardiomyopathy
CK levels 10x normal
Onset before the age of 5
Wheelchair bound before 13
Death in their 30’s
Absence of Dystrophin

Question 21

Clinical manifestations of Becker (7)

Answer 21

Progressive muscular weakness proximal > distal
Dilated cardiomyopathy
CK levels 5x normal
Later onset
Wheelchair bound after 16
Death in their 40’s
Abnormal quantity or quality of Dystrophin

Question 22

DMD-associated DCM

Answer 22

Dilated cardiomyopathy presenting between 20-40 years of age
Early death
No skeletal muscle involvement
No Dystrophin in the myocardium

Question 23

What percentage of Hemophilia A carrier females are affected?

Answer 23

10%

Question 24

Clinical manifestations of Hemophilia A

Answer 24

Blood disorder where blood fails to clot appropriately due to a deficiency of Factor VIII
Spontaneous bleeds into joints, muscles or intracranial
Excessive bruising
Prolonged bleeding after injury or incision
Delayed wound healing

Question 25

Gene mutation of Hemophilia A

Answer 25

F8 | Encoding for Factor VIII

Question 26

Chromosome location for Hemophilia A mutation

Answer 26

Xq28 | 22A inversion causes 50%

Question 27

How many genes does mtDNA encode?

Answer 27

37

Question 28

Mitochondrial DNA mutation diseases (4)

Answer 28

Kearnes-Sayre MELAS MERFF Leber Hereditary Optic Neuropathy

Question 29

Clinical manifestations of Kearnes-Sayre (7)

Answer 29

``` Triad: Pigmentary Retinopathy Progressive External Ophthalmoplegia And onset before age 20y Cardiac conduction defects Ataxia Deafness Kidney problems ```

Question 30

MELAS and MERFF have a high or low new mutation?

Answer 30

Low

Question 31

Clinical manifestations of MELAS (5)

Answer 31

``` Starts between age 2 & 10 y Muscle weakness Seizures Repetitive stroke-like episodes Elevated lactic acidosis ```

Question 32

Most common gene mutation in MELAS

Answer 32

MT-TL1 (80%)

Question 33

MERRF clinical manifestations (5)

Answer 33

``` Muscle symptoms Seizures Ataxia Dementia Ragged-red fibers ```

Question 34

Gene mutation for MERFF

Answer 34

MT-TK

Question 35

Clinical manifestations of Leber hereditary Optic Neuropathy

Answer 35

Bilateral subacute vision failure | Occurs during young adulthood