Nonclassical Chromosomal disorders

Fragile X syndrome

Transcriptional silencing (loss of function) mutation

Loss of RNA binding = impaired translational repression of target RNAs

(CGG) n> 200

Fragile C tremor / ataxia syndrome

2 to 5 fold increase in FMR1 and mRNA

neuronal intranuclear inclusions

CGG n60-200

Friedreich ataxia

Impaired transcriptional elongation

loss of fraxtaxin function

Increased Fe in mitochondria

reduced heme synthesis

GAA n>200

Myotonic dystrophy 2

CCTG n>75

confer novel properties of RNA

increase amounts of RNA binding proteins → impaired RNA splicing of key proteins

Huntington’s disease

CAG n>40

novel properties on huntington’s protein

Trisomy 21

Down syndrome

mental delays

abundant neck skin

congenital heart defects

intestinal stenosis

Umbilical hernia

Trisomy 18

Edwards syndrome

mental delays

micrognathis

congenital heart defects

renal malformations

rocker-bottom feet

Trisomy 13

Patau syndrome

Cleft lip

microcephaly (developmental delays)

polydactyly

microphthalmia

cardiac defects