TNR Disorders Flashcards
TNR Instabilities
Tissues Nucleotide sequence Development Environmental/epigenetic cues Sex
Misfolded protein diseases
Hungtingtons
Spinocerebellar ataxia
Diminished or absent protein diseases
Freidrich’s ataxia
Fragile X syndrome
Genetic anticipation
The more repeats you have, the younger you will present with symptoms, and the more severe they will be
Huntingtons Chorea Symtpoms
Saccadic eye movement
Increased muscle tone
Ataxic gait
Choreatic movements
Huntingtons epidemiology
Autosomal Dominant
First exon mutation that causes increase in Glu’s
Causes aggregate protein
Huntingtons molecular genetics
Paternal transmission
Occurs through spermatogenesis
Normal HD Gene
6-35 repeats
Pre mutation HD Gene
36-39 repeats
HD Disease phenotype
> 39 repeats
HD detection tools
PCR analysis to compare protein lengths
Fragile X Epidemiology
X linked Recessive
Most common cause of inherited retardation
CGG expansion in the 5’ promoter region of FMR1
Maternal transmission
Fragile X symptoms
Cognitive disability
Long face, large ears
Large testes in 90% males
FMR1 pre mutation phenotype
Cessation of menses before 40
Fredrich’s Ataxia epidemiology
Autosomal Recessive
Expansion of GAA in first intron in FRDA gene (mitochondrial protein)
Results in transcript loss due to misplicing and degradation
Freidrich’s Ataxia Symptoms
Defective iron metabolism, defective mitochondria Cell loss in high energy tissues Diabetes Ataxic gait, dysarthria, dysphasia Cognitive dysfunction
Myotonic Dystrophy Epidemiology
Autosomal Dominant
Expansion of CTG in 3’ UTR of DMPK gene
Most common cause of muscular dystrophy
Inheritance of MD Type 1
Congenital= mother
Anything else can be both up to 1000 repeats, then only mom
Pronounced anticipation
MD mechanism
Repeats cause large hairpin sequences in 3’ region that halt translation
Congenital is almost always mother
MD symptoms
Muscular dystrophy
Myotonia
Type 2 diabetes
Cardiomyopathy
