Keratin 8 mutations are risk factors for developing liver...

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

Reexamination Certificate

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C435S004000, C435S007100, C435S091200, C530S350000, C530S357000, C536S023500, C536S024310

Reexamination Certificate

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07838217

ABSTRACT:
Keratin 8 and 18 (K8/K18) mutations are shown to be associated with a predisposition to liver or biliary tract disease, particularly noncryptogenic hepatobiliary disease. Unique K8/K18 mutations are shown in patients with diseases including but without limitation to viral hepatitis, biliary atresia, alcoholic cirrhosis and other acute or chronic toxic liver injury, cryptogenic cirrhosis, acute fulminant hepatitis, autoimmune liver disease, cystic fibrosis, primary biliary cirrhosis, primary sclerosing cholangitis, diseases that are linked with cryptogenic cirrhosis, such as nonalcoholic steatohepatitis, and the like. Livers with keratin mutations had increased incidence of cytoplasmic filamentous deposits. Therefore, K8/K18 are susceptibility genes for developing cryptogenic and noncryptogenic forms of liver disease. Mutant alleles are associated with disease susceptibility, and their detection is used in the diagnosis of a predisposition to these conditions.

REFERENCES:
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Strnad, P., et al., “Keratin variants associate with progression of fibrosis during chronic Hepatitis C infection,” (2006)The American Association for the Study of Liver Disease, published online in Wiley InterScience (www.interscience.wiley.com).
Ku et al., Keratin Mutations Predispose to Cryptogenic and Noncryptogenic Liver Disease, Gastroenterology, 2002, 122(4): Suppl. 1, p. 80.
Ku et al., Keratin 8 and 18 Mutations Associate With a Broad Range of Human Liver Diseases, Molecular Biology of the Cell, 2001, 12: supplement, p. 56A.
Ku et al., Keratin 8 Mutations in Patients With Cryptogenic Liver Disease, The New England J. of Med., 2001, 344(21): 1580-1587.
Ku et al., Keratin 8 and 18 Mutations Are Risk Factors for Developing Liver Disease of Multiple Etiologies, PNAS, 2003, 100(10): 6063-6068.
Irvine, A., et al., “Human keratin diseases: the increasing spectrum of disease and subtlety of the phenotype-genotype correlation,” (1999)British Journal of Dermatology, 140:815-828.
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Genbank Accession No. NM—002273 Nov. 18, 2006.

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