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TTR

MIM.176300 18q11.2-q12.1

Tuesday 5 February 2008

Transthyretin (TTR) is a homotetrameric protein with a prominent beta-sheet secondary structure.

Pathology

Approximately 80 different mutations in transthyretin have been reported. A few mutations are not associated with amyloidosis, and a couple are thought to protect against the deposition of amyloid.

The Thr119Met variant of transthyretin (TTR) has a thermodynamic stabilizing effect on transthyretin tetramers in association with both the wild-type polypeptide (wild type/Met119 genotype) and the amyloidogenic variant Val30Met.

Persons with transthyretin tetramers reflecting the Met30/Met119 genotype are protected from the disease that occurs in those with the Met30/wild-type genotype.

The folding stability of the newly identified Thr70Asn variant of lysozyme is between that of normal and amyloidogenic species.

However, although destabilized, this molecule is not amyloidogenic, which suggests that certain proteins have a marginal degree of protection against amyloidogenesis, even when their thermodynamic stability is less than that of wild-type protein.

- amyloid polyneuropathy

  • Swedish type amyloid polyneuropathy
  • Portuguese type amyloid polyneuropathy
  • Japanese type amyloid polyneuropathy
  • Jewish type amyloid polyneuropathy
  • Maryland type amyloid polyneuropathy
  • Mahloudji type amyloid polyneuropathy
  • Appalachian type amyloid polyneuropathy
  • German-american type amyloid polyneuropathy
  • Indiana or Rukavina type amyloid polyneuropathy

- cardiac amyloidosis (amyloidosis type III)
- senile systemic amyloidosis
- senile cardiac amyloidosis
- familial amyloidosis
- carpal tunnel syndrome by amyloidosis
- leptomeningeal amyloidosis (MIM.105210)
- oculoleptomeningeal amyloidosis (MIM.105210)

- familial euthyroid hyperthyroxinemia

References

- Jacob, E. K., Edwards, W. D., Zucker, M., D’Cruz, C., Seshan, S. V., Crow, F. W., Highsmith, W. E. (2007). Homozygous Transthyretin Mutation in an African American Male. J. Mol. Diagn. 9: 127-131

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