Diseases That Result from Expansion of Trinucleotide Repeats

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Diseases That Result from Expansion of
Trinucleotide Repeats

• Type? trinucleotide repeat diseases
• xuyan

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Type? diseases differ from the Type?disease
Type?disease Type?diseases
Repeating trinucleotide unit CAG A variety of trinucleotides,
Encode amino acids Yes (Glu) No
Quantity of trinucleotide repeats Exceed 35 Glu Massive repeats(gt200)
Affected part Brain Numerous of body
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• The best studied Type?diseases is fragile X
  syndrome(X????????) ,so named because the mutant
  X chromosome is especially susceptible(?????) to
  damage.

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• The fragile X syndrome is the most common form of
  inherited mental retardation(????) and accounts
  for approximately 40 of cases with X-linked
  mental retardation. 

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• Other characteristics of the fragile X syndrome
  include a wide range of cognitive(???),
  behavioral(???), and physical features such as
  variable IQ (profound to mild mental
  retardation), autistic-like(??????) features,
  hyperactivity(????), increased testicular
  (??)volume, macrocephaly(???), and large ears.  .
  

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• The fragile X mental retardation-1 (FMR1) gene
  codes for the mRNA-binding fragile X mental
  retardation protein (FMRP).
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• FMRP is normally made in many tissues, especially
  in the brain and testes(??).

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Where is the FMR1 gene located?

• The FMR1 gene is located on the long (q) arm of
  the X chromosome at position 27.3.
• Cytogenetic Location Xq27.3

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• Almost all cases of fragile X syndrome are caused
  by expansion of the CGG trinucleotide repeat in
  the FMR1 gene. In these cases, CGG is abnormally
  repeated from 200 to more than 1,000 times, which
  makes this region of the gene unstable.

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• A normal allele of FMR1 gene contains anywhere
  that is repeated in a part of the gene that
  corresponds to the 5 noncoding portion of the
  messenger RNA (Figure 1).

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Figure 1
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• The CGG repeat in FMR1 that can be categorized
  into three classes based on the size of the
  repeat normal (5-55 repeats), premutation
  (60-200 repeats), and full mutation (200-2000
  repeats).  The full mutation is the
  disorder-causing form of the repeat, and the
  premutation is the carrier form of the repeat. 

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• Full mutations result in hypermethylation of the
  DNA in and around the CGG tract, curtailed gene
  expression and no FMRP being produced.

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• Without adequate FMRP, severe learning problems
  or mental retardation and the other features of
  fragile X syndrome can developed.

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• Smaller expansions of the CGG repeat, or
  premutations, do not cause Fragile X syndrome
  but may show expansion into full mutations over
  one or more generations.

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• Unlike an abnormal HD allele, FMR1 allele causes
  disease as the result of a gain of function , an
  abnormal FMR1 allele causes disease as the result
  of a loss of function .

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Conclusion

• The fragile X syndrome is the best studied
  Type?diseases ,which is a X-linked disease .The
  most characteristic of the fragile X syndrome is
  mental retardation. Almost all cases of fragile X
  syndrome are caused by expansion of the CGG
  repeat in the FMR1 gene. In these cases, CGG is
  abnormally repeated from 200 to more than 1,000
  times

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• Although there is no effective treatment for
  any of the disease caused by trinucleotide
  expansion, the risk of transmitting or possessing
  a mutant allele can be assessed through genetic
  screening.

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Thank you!