scholarly journals Identification of Novel Mutations in FAH Gene and Prenatal Diagnosis of Tyrosinemia in Indian Family

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Jayesh J. Sheth ◽  
Chitra M. Ankleshwaria ◽  
Rajeshwari Pawar ◽  
Frenny J. Sheth
Keyword(s):  
Prenatal Diagnosis ◽  
Secondary Structure ◽  
Point Mutation ◽  
Splice Site ◽  
Experimental Program ◽  
Type I ◽  
Novel Mutations ◽  
Potential Donor ◽  
Tyrosinemia Type I ◽  
Fumarylacetoacetate Hydrolase

Carrier of tyrosinemia type I was diagnosed by sequencingFAH(fumarylacetoacetate hydrolase) gene. It leads to the identification of heterozygous status for both c.648C>G (p.Ile216Met) and c.1159G>A (p.Gly387Arg) mutations in exons 8 and 13, respectively, in the parents. The experimental program PolyPhen, SIFT, and MT predicts former missense point mutation as “benign” that creates a potential donor splice site and later one as “probably damaging” which disrupts secondary structure of protein.

Tyrosinemia type I—Diagnostic issues and prenatal diagnosis

2006 ◽  
Vol 73 (2) ◽  
pp. 163-165 ◽  
Author(s):  
Sunita Bijarnia ◽  
Ratna D. Puri ◽  
Jean Ruel ◽  
George F. Gray ◽  
Linda Jenkinson ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Type I ◽  
Tyrosinemia Type I

A Single Mutation of the Fumarylacetoacetate Hydrolase Gene in French Canadians with Hereditary Tyrosinemia Type I

1994 ◽  
Vol 331 (6) ◽  
pp. 353-357 ◽  
Author(s):  
Markus Grompe ◽  
Maryse St.-Louis ◽  
Sylvie I. Demers ◽  
Muhsen Al-Dhalimy ◽  
Barbara Leclerc ◽  
...  
Keyword(s):  
Type I ◽  
Single Mutation ◽  
French Canadians ◽  
Tyrosinemia Type I ◽  
Fumarylacetoacetate Hydrolase ◽  
Hereditary Tyrosinemia

scholarly journals Hereditary tyrosinemia type I–associated mutations in fumarylacetoacetate hydrolase reduce the enzyme stability and increase its aggregation rate

2019 ◽  
Vol 294 (35) ◽  
pp. 13051-13060 ◽  
Author(s):  
Iratxe Macias ◽  
Ana Laín ◽  
Ganeko Bernardo-Seisdedos ◽  
David Gil ◽  
Esperanza Gonzalez ◽  
...  
Keyword(s):  
Enzyme Stability ◽  
Type I ◽  
Aggregation Rate ◽  
Tyrosinemia Type I ◽  
Fumarylacetoacetate Hydrolase ◽  
Hereditary Tyrosinemia

Two novel mutations involved in hereditary tyrosinemia type I

1995 ◽  
Vol 4 (2) ◽  
pp. 319-320 ◽  
Author(s):  
Maryse St-Louis ◽  
Jacques Poudrier ◽  
Daniel Phaneuf ◽  
Barbara Lecierc ◽  
Rachel Laframboise ◽  
...  
Keyword(s):  
Type I ◽  
Novel Mutations ◽  
Tyrosinemia Type I ◽  
Hereditary Tyrosinemia

scholarly journals Therapeutic Targeting of Fumaryl Acetoacetate Hydrolase in Hereditary Tyrosinemia Type I

2021 ◽  
Vol 22 (4) ◽  
pp. 1789
Author(s):  
Jon Gil-Martínez ◽  
Iratxe Macias ◽  
Luca Unione ◽  
Ganeko Bernardo-Seisdedos ◽  
Fernando Lopitz-Otsoa ◽  
...  
Keyword(s):  
Autosomal Recessive Disorder ◽  
Type I ◽  
Secondary Effects ◽  
Pharmacological Chaperones ◽  
Liver And Kidney ◽  
Tyrosinemia Type I ◽  
Fumarylacetoacetate Hydrolase ◽  
Hereditary Tyrosinemia ◽  
First Time

Fumarylacetoacetate hydrolase (FAH) is the fifth enzyme in the tyrosine catabolism pathway. A deficiency in human FAH leads to hereditary tyrosinemia type I (HT1), an autosomal recessive disorder that results in the accumulation of toxic metabolites such as succinylacetone, maleylacetoacetate, and fumarylacetoacetate in the liver and kidney, among other tissues. The disease is severe and, when untreated, it can lead to death. A low tyrosine diet combined with the herbicidal nitisinone constitutes the only available therapy, but this treatment is not devoid of secondary effects and long-term complications. In this study, we targeted FAH for the first-time to discover new chemical modulators that act as pharmacological chaperones, directly associating with this enzyme. After screening several thousand compounds and subsequent chemical redesign, we found a set of reversible inhibitors that associate with FAH close to the active site and stabilize the (active) dimeric species, as demonstrated by NMR spectroscopy. Importantly, the inhibitors are also able to partially restore the normal phenotype in a newly developed cellular model of HT1.

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