Neuro,Mitochondria,Microdeletions

Question 1

Alzheimer disease gene/chr mutation.

Answer 1

• APP gene (Amyloid Precursor Protein)

- chr21

Question 2

Usual (late) onset DZ associated with what gene/allele.

Answer 2

-APOE gene (E4 allele)

Question 3

Pick disease (frontotemporal dementia with Parkinsoniasm) gene mutation and protein.

Answer 3

• MAPT gene

- Microtubule Associated Protein Tau

Question 4

Familial cases of Parkinson disease and Lewy body disease spectrum are ass. w/ anomalies in which genes?

Answer 4

PARK1 through PARK8

Question 5

Huntington Disease genetics (inheritance/trinucloetide repeat/gene/chr).

Answer 5

• Autosomal Dominant
• CAG repeats
• HTT gene on chr4p

Question 6

In Huntington Dz what number of repeats is considered a Premutation?

Answer 6

28-35

<28 is normal phenotype

Question 7

In Huntington Dz what number of repeats is associated with disease?

Answer 7

> 40

Question 8

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarctions and Leukoencephalopathy (CADASIL) gene mutation.

Answer 8

NOTCH3

Question 9

Histology of CADASIL.

Answer 9

Vessels with granular eosinophilic medial deposits.

affected vessels may be found in skin

Question 10

Autosomal Dominant disorder caused by duplication of a 1.5Mb region of DNA on chr17 containing the PMP22 gene.

Answer 10

Charcot-Marie-Tooth

Question 11

What does Charcot-Marie-Tooth affect and what are the histological findings?

Answer 11

• Sensory and Motor neurons

- Onion Bulb formation

Question 12

Autosomal Recessive disease associated with Lower Motor Neuron deficits.

Answer 12

Spinal Muscular Atrophy (SMA)

Question 13

What is the most severe form of Spinal Muscular Atrophy?

Answer 13

SMA type I

-Werdnig-Hoffman disease

Question 14

What mutation is involved in all cases of Spinal Muscular Atrophy?

Answer 14

SMN1 gene (survival motor neuron 1)

Question 15

Dystrophinopathies (Duchenne and Becker) gene/chr/inheritance.

Answer 15

• DMD gene on Xp21.2

- X linked recessive (1/3 are sporadic)

Question 16

Myotonic Muscular Dystrophy genetics.

Answer 16

Autosomal Dominant

-Trinucleotide Repeat Disorder

Question 17

Genetics of Malignant Hyperthermia (MH).

Answer 17

RYR1 calcium channel defect

Question 18

What is the 1st sign of Malignant Hyperthermia?

Answer 18

Hypercarbia while under anasthesia

Question 19

Mitochondrial disorders:

-Typical findings

Answer 19

• Optalmoplegia
• Ptosis
• Retinopathy
• Skeletal Myopathy
• Cardiomyopathy
• Sensorineural Deafness
• Encephalopathy

Question 20

Screening tests for Mitochondrial disorders.

Answer 20

• Lactic Acid (plasma or CSF)
• Ketones
• Acylcarnitines
• Urinary organic acids

Question 21

Characteristic muscle biopsy findings in Mitochondrial disorders.

Answer 21

• Ragged red fibers (trichrome)

- “Parking Lot” inclusions (EM)

Question 22

Two syndromes caused by major structural defects–gross deletions or large rearrangements–in mtDNA.

Answer 22

• Kearns-Sayre syndrome

- Pearson syndrome

Question 23

Syndrome characterized by progressive neurologic deterioration after initially normal development.

Answer 23

MELAS

-Mitochondrial Encephalopathy with Lactic Acidosis and Strokelike episodes

Question 24

MELAS genetics.

Answer 24

MT-TLI gene point mutations

-located within the mtDNA

Question 25

Microdeletion syndrome:

- Abnormal cry, microcephaly, MR

Answer 25

Cri du chat (5p15)

Question 26

Microdeletion syndrome:

- Hyperphagia, obesity, hypogonadism, mild MR

Answer 26

Prader-Willi (Paternal; 15q11)

Question 27

Microdeletion syndrome:

- Anosmia, hypogonadism

Answer 27

Kallman (Xp22.3)

Question 28

Microdeletion syndrome:

-Hyperactivity, inappropriate laughter, aphasia, ataxia, MR, seizures

Answer 28

Angelman (Maternal; 15p11)

Question 29

Microdeletion syndrome:

-CHARGE sequence manifestations

Answer 29

• Coloboma
• Cardiac malformation
• Choanal atresia
• Genital hypoplasia
• Deafness
• MR

Question 30

Microdeletion syndrome Abberations:

- DiGeorge, Catch 22, CHARGE, velo-cardiofacial

Answer 30

22q11.2

Question 31

Microdeletion syndrome Abberations:

- Cri du chat

Answer 31

5p15

Question 32

Microdeletion syndrome Abberations:

- Kallman

Answer 32

Xp22.3

Question 33

Microdeletion syndrome Abberations:

- Prader-Willi

Answer 33

15q11.2 (PATERNAL)

Question 34

Microdeletion syndrome Abberations:

- Angelman

Answer 34

15q11.2 (MATERNAL)

Question 35

Microdeletion syndrome Abberations:

- Williams syndrome (Elfinlike facies, infantile hypercalcemia)

Answer 35

7q11