Abstract
Tyrosinemia type I (OMIM 276700) is a rare, autosomal recessive disorder caused by a deficiency in the fumarylacetoacetate hydrolase (FAH) enzyme. This study examined the spectrum of FAH gene mutation in 32 patients with tyrosinemia type I. In addition, clinical and biochemical findings were evaluated to establish a genotype–phenotype relationship in the patients. Mutation screening was performed using a 50K custom-designed resequencing microarray chip (TR_06_01r520489, Affymetrix) and sequencing analysis. Of the 12 different mutations found, 6 are categorized as novel. Three of the mutations-IVS6-1G>A, D233V, and IVS3-3C>G-are the most common in Turkish patients, comprising 25%, 17.1%, and 12.5% of mutant alleles, respectively.
Clinical evaluations suggest that the spectrum of symptoms observed in the patients with very early and early disease were of the more nonspecific form, whereas the patients with late-presenting disease had more of the distinctive form over the course of the disease. This study adds support to the notion that the D233V mutation is specific to the Turkish population.
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Acknowledgement
This study was supported by the State Planning Organization of Turkey (project No: DPT 2006K120640).
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Synopsis
Synopsis
The article describes different type of FAH mutations and their clinical outcomes in tyrosinemia type 1 patients.
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Dursun, A. et al. (2011). Mutation Spectrum of Fumarylacetoacetase Gene and Clinical Aspects of Tyrosinemia Type I Disease. In: JIMD Reports - Case and Research Reports, 2011/1. JIMD Reports, vol 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_10
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DOI: https://doi.org/10.1007/8904_2011_10
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