The mutation spectrum and ethnic distribution of non-hepatorenal tyrosinemia (types II, III)

Orphanet Journal of Rare Diseases

Review

Sara Karimzadeh¹  Zahra Beyzaei²  Sara Nabavizadeh²  Bita Geramizadeh³ 

[1] Shiraz Medical School Library, Shiraz University of Medical Sciences, Shiraz, Iran;Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;Department of Pathology, Medical School of Shiraz University, Shiraz Transplant Research Center (STRC), Shiraz University of Medical Sciences, Khalili St., Research Tower, Seventh Floor, Shiraz, Iran;

关键词: Tyrosinemia;    Genotype;    Mutations;    Tyrosine aminotransferase;    4-Hydroxyphenylpyruvate dioxygenase;   

DOI  :  10.1186/s13023-022-02579-0

 received in 2022-08-24, accepted in 2022-11-20,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundDifferent types of non-hepatorenal tyrosinemia are among the rare forms of tyrosinemia. Tyrosinemia type II and III are autosomal recessive disorders caused by pathogenic variants in the tyrosine aminotransferase (TAT), and 4-hydroxyphenyl-pyruvate dioxygenas (HPPD) genes, respectively. There are still unclarified aspects in their clinical presentations, mutational spectrum, and genotype–phenotype correlation.Main bodyIn this study, we evaluated the spectrum of TAT and HHPD gene mutations in patients with tyrosinemia type II and III. Moreover, biochemical and clinical findings are evaluated to establish a genotype–phenotype relationship in the above-mentioned patients. Thirty-three TAT variants have been reported in 42 families, consisting of 21 missense variants, 5 frameshift variants, 4 nonsense variants, 2 variants that primarily cause splicing site, and 1 skipping complete exon (large deletion). The most common variant is p.Arg57Ter, causing a splicing defect, and resulting in premature termination of translation, which was found in 10 patients from 3 families. In HPPD gene, eleven variants in 16 patients have been reported including 7 missense variants, 2 nonsense variants, 1 splice defect, and 1 frameshift variant so far. All variants are unique, except for p.Tyr160Cys, which is a missense variant found in two different patients. Regarding genotype–phenotype correlations, in 90% of tyrosinemia type II patients, positive clinical and biochemical correlations with a detected variant are observed. In HPPD gene, due to the small number of patients, it is not possible to make a definite conclusion.ConclusionThis is the first large review of variants in TAT and HPPD, highlighting the wide spectrum of disease-causing mutations. Such information is beneficial for the establishment of a privileged mutation screening process in a specific region or ethnic group.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

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Fig. 7