1-34 Trinucleotide repeat disorders Flashcards
Fragile X Syndrome
phenotype: some types of faces
probability of intellectual disability increases with each generation
CGG trinucleotide repeats expansion leads to methylation of the CpG island and repressed FMR1
has a propensity to expand during oogenesis, premutations and meiotically unstable and mitotically stable (25-200 repeats) full mutations are meiotically and mitotically unstable
NOT X LINKED Recessive
anticipation
more frequently describes a trait in later generations ex: fragile X
or at an earlier age in subsequent generations
fragile X premutation carriers
heterozygotes of premutation levels still have some type of later life phenotypes
Friedreich’s ataxia
most common inherited atazia, intron of frataxin gene, expansion of GAA repeat
ataxia of all limbs, glucose intolerance, progressive condition, number of repeats assosiated with earlier disease onset
ANTICIPATION
myotonic distrophy
autosomal dominant
CTG repeat in 3’ UTR of protein kinase
correlation of repeat length and severity
Complete Androgen Insensitivity Syndrome
“Testicular feminization”
mutation in the androgen receptor (X linked), affects only 46, XY males = sex limited
normal female external genitalia, blind vagina, female looking body
lack of response to androgen results in absence of pubic, axillary and facial hair, no neurologic disease, has male levels of testosterone
SBMA Kennedy Disease
slow progressive loss of spinal cord and bulbar motor neurons
develops breasts in males
progressive weakness throughout life span
exon 1 of X chromosome has a trinuc expansion, gain of function effect, expansion happens in male meioses mostly,
Summary of trinuc diseases
loss of function: fragile X, friedreich ataxia
gain of function: production of RNA with expanded tract and sequestartion of other proteins (Myotonic dystrophy, graile X)
Gain of function: protein with expanded polyglutamine tract: Huntington, SBMA
Gain of function: protein with expanded polyalanine tract
