Mutational spectrum of Mexican patients with tyrosinemia type 1: In silico modeling and predicted pathogenic effect of a novel missense FAH variant.

ABSTRACT:

Background

Tyrosinemia type 1 (HT1, MIM#276700) is caused by a deficiency in fumarylacetoacetate hydrolase (FAH) and it is associated with severe liver and renal disfunction. At present, the mutational FAH (15q25.1, MIM*613871) spectrum underlying HT1 in the Mexican population is unknown. The objective of this study was to determine the FAH genotypes in eight nonrelated Mexican patients with HT1, who were diagnosed clinically.

Methods

Sequencing of FAH and their exon-intron boundaries and in silico protein modeling based on the crystallographic structure of mouse FAH.

Results

We identified pathogenic variants in 15/16 studied alleles (93.8%). Nine different variants were found. The most commonly detected HT1-causing allele was NM_000137.2(FAH):c.3G > A or p.(?) [rs766

SUBMITTER: Ibarra-Gonzalez I 

PROVIDER: S-EPMC6900384 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature