- Human pathology

Home > A. Molecular pathology > translation diseases

translation diseases

Saturday 4 February 2006

Definition: Pathology of RNA translation.

The list of genetic diseases caused by mutations that affect mRNA translation is rapidly growing. Although protein synthesis is a fundamental process in all cells, the disease phenotypes show a surprising degree of heterogeneity.

Studies of some of these diseases have provided intriguing new insights into the functions of proteins involved in the process of translation; for example, evidence suggests that several have other functions in addition to their roles in translation.

Given the numerous proteins involved in mRNA translation, it is likely that further inherited diseases will turn out to be caused by mutations in genes that are involved in this complex process.

Wolcott-Rallison syndrome

Mutation of a kinase that regulates translation initiation has been implicated in the etiology of a monogenic form of diabetes known as Wolcott-Rallison syndrome.

Defective translation initiation causes vanishing of cerebral white matter (VCWM) (16545608)

Type 2 diabetes

Type 2 diabetes is a polygenic disorder characterized by multiple biochemical defects including transcriptional, translational, and posttranslational abnormalities. Although major progress has been made in elucidation of factors at the transcriptional and posttranslational levels, defects at the translational level remain elusive.

Recent progress in the understanding of endoplasmic reticulum overload by unfolded proteins has begun to uncover mechanisms leading to pancreatic beta-cell exhaustion.

Future advances in this area may lead to identification of the missing links in the pathogenesis of beta-cell failures due to conditions such as hyperinsulinemia, hyperglycemia, and long-term treatment with sulfonylureas, and thus may identify novel therapeutic targets for diabetes.

Mouse models

Characterization of mice rendered deficient in eukaryotic initiation factors has provided model systems to study the involvement of translation in regulating insulin synthesis and secretion, hepatic function, peripheral insulin resistance, and diabetic complications.

See also

- Reticulum endoplasmic

  • reticulum endoplasmic stress


- Scheper GC, van der Knaap MS, Proud CG. Translation matters: protein synthesis defects in inherited disease. Nat Rev Genet. 2007 Sep;8(9):711-23. PMID: 17680008

- Brickwood S, Bonthron DT, Al-Gazali LI, Piper K, Hearn T, Wilson DI, Hanley NA. Wolcott-Rallison syndrome: pathogenic insights into neonatal diabetes from new mutation and expression studies of EIF2AK3. J Med Genet. 2003 Sep;40(9):685-9. PMID: 12960215

- Shi Y, Taylor SI, Tan SL, Sonenberg N. When translation meets metabolism: multiple links to diabetes. Endocr Rev. 2003 Feb;24(1):91-101. PMID: 12588811

- Harding HP, Ron D. Endoplasmic reticulum stress and the development of diabetes: a review. Diabetes. 2002 Dec;51 Suppl 3:S455-61. PMID: 12475790

- Scheper GC, Proud CG, van der Knaap MS. Defective translation initiation causes vanishing of cerebral white matter. Trends Mol Med. 2006 Apr;12(4):159-66. PMID: 16545608

- Stoneley M, Willis AE. Aberrant regulation of translation initiation in tumorigenesis. Curr Mol Med. 2003 Nov;3(7):597-603. PMID: 14601635

- Calkhoven CF, Muller C, Leutz A. Translational control of gene expression and disease. Trends Mol Med. 2002 Dec;8(12):577-83. PMID: 12470991

- Mendez R, Wells D. Location, location, location: translational control in development and neurobiology. Trends Cell Biol. 2002 Sep;12(9):407-9. PMID: 12220852