Fragile X Flashcards
What is the fragile x gen and protein
FRM1 and FRMP
Where is FRM1 located
Xq27.3
What is fragile x mode of inheritance
XLD x linked dominant disease
What is the incidence of fragile x
Males 1:4000
Females 1:8000
Describe the expansion
Unstable CGG repeat in the 5’utr
Contains AGG inspersons in normal person 9-10 repeats appart adding to stability. Loss or conversion adds to instability
What is the disease mechanism
Lack of FRMP protein
Describe the clinical features
Severe intellectual disability, social impairment, large head, long face, large protruding ears, prominent forehead and chin, joint laxity, macro-orchidism
In females: 50% normal to mild mental or social impairment, varies due to skewed x inactivation
What is full mutation range and how does it cause disease
> 200 repeats leading to hypermethylation of surrounding region inhibiting gene expression. 20% also show mosaic is for premutation
What is the normal range of repeats
6-50
What is the range of intermediate alleles
46-58rpts
What is the premutation range
55-200rpts
Describe POI
POI - occurs in 20% of females wi5 a permutation, cessation of menses before 40 and menopause approx. 5 years early. Greater risk in 80-100rpt range than above 100.
Increased rna levels but no change to protein levels.
Describe FXTAS
Late onset cerebella’s ataxia and tremor in males with a premutation. Penetrance is 75% at age 80 and age of onset correlates with number of repeats
Females also affected
Describe premutations
59-200 repeats mostly lacking AGG inspersons
Unmethylated
Conversion to full mutation probability is low for 59-70rpts but >90%for >90rpts
Describe FRAXE
FMR2 gêne, Xq28
Expansion of GCC tract
Less severe phenotype
No premutation phenotype
Lower prevalence
