TNR Disorders

Question 1

TNR Instabilities

Answer 1

Tissues 
Nucleotide sequence
Development 
Environmental/epigenetic cues
Sex

Question 2

Misfolded protein diseases

Answer 2

Hungtingtons

Spinocerebellar ataxia

Question 3

Diminished or absent protein diseases

Answer 3

Freidrich’s ataxia

Fragile X syndrome

Question 4

Genetic anticipation

Answer 4

The more repeats you have, the younger you will present with symptoms, and the more severe they will be

Question 5

Huntingtons Chorea Symtpoms

Answer 5

Saccadic eye movement
Increased muscle tone
Ataxic gait
Choreatic movements

Question 6

Huntingtons epidemiology

Answer 6

Autosomal Dominant
First exon mutation that causes increase in Glu’s
Causes aggregate protein

Question 7

Huntingtons molecular genetics

Answer 7

Paternal transmission

Occurs through spermatogenesis

Question 8

Normal HD Gene

Answer 8

6-35 repeats

Question 9

Pre mutation HD Gene

Answer 9

36-39 repeats

Question 10

HD Disease phenotype

Answer 10

> 39 repeats

Question 11

HD detection tools

Answer 11

PCR analysis to compare protein lengths

Question 12

Fragile X Epidemiology

Answer 12

X linked Recessive
Most common cause of inherited retardation
CGG expansion in the 5’ promoter region of FMR1
Maternal transmission

Question 13

Fragile X symptoms

Answer 13

Cognitive disability
Long face, large ears
Large testes in 90% males

Question 14

FMR1 pre mutation phenotype

Answer 14

Cessation of menses before 40

Question 15

Fredrich’s Ataxia epidemiology

Answer 15

Autosomal Recessive
Expansion of GAA in first intron in FRDA gene (mitochondrial protein)
Results in transcript loss due to misplicing and degradation

Question 16

Freidrich’s Ataxia Symptoms

Answer 16

Defective iron metabolism, defective mitochondria 
Cell loss in high energy tissues 
Diabetes 
Ataxic gait, dysarthria, dysphasia 
Cognitive dysfunction

Question 17

Myotonic Dystrophy Epidemiology

Answer 17

Autosomal Dominant
Expansion of CTG in 3’ UTR of DMPK gene
Most common cause of muscular dystrophy

Question 18

Inheritance of MD Type 1

Answer 18

Congenital= mother
Anything else can be both up to 1000 repeats, then only mom
Pronounced anticipation

Question 19

MD mechanism

Answer 19

Repeats cause large hairpin sequences in 3’ region that halt translation
Congenital is almost always mother

Question 20

MD symptoms

Answer 20

Muscular dystrophy
Myotonia
Type 2 diabetes
Cardiomyopathy