The Unique Spectrum of Mutations in Patients with Hereditary Tyrosinemia Type 1 in Different Regions of the Russian Federation.

Autor: Baydakova GV; Federal State Budgetary Scientific Institution 'Research Center for Medical Genetics', Moscow, Russia., Ivanova TA; Federal State Budgetary Scientific Institution 'Research Center for Medical Genetics', Moscow, Russia. breaking18@gmail.com., Mikhaylova SV; Russian Children's Clinical Hospital of the Ministry of Health of the Russian Federation, Moscow, Russia., Saydaeva DK; Perinatal Center, State Budgetary Institution Maternity Hospital, Grozny, The Chechen Republic, Russia., Dzhudinova LL; Perinatal Center, State Budgetary Institution Maternity Hospital, Grozny, The Chechen Republic, Russia., Akhlakova AI; Republican Center for Medical Genetics, Makhachkala, The Republic of Dagestan, Russia., Gamzatova AI; Republican Center for Medical Genetics, Makhachkala, The Republic of Dagestan, Russia., Bychkov IO; Federal State Budgetary Scientific Institution 'Research Center for Medical Genetics', Moscow, Russia., Zakharova EY; Federal State Budgetary Scientific Institution 'Research Center for Medical Genetics', Moscow, Russia.
Jazyk: angličtina
Zdroj: JIMD reports [JIMD Rep] 2019; Vol. 45, pp. 89-93. Date of Electronic Publication: 2018 Nov 11.
DOI: 10.1007/8904_2018_144
Abstrakt: Background: Hereditary tyrosinemia (HT1) is an autosomal recessive disorder characterized by impaired tyrosine catabolism because of fumarylacetoacetate hydrolase deficiency. HT1 is caused by homozygous or compound heterozygous mutations in the FAH gene. The HT1 frequency worldwide is 1:100,000-1:120,000 live births. The frequency of HT1 in the Russian Federation is unknown.
Aim: To estimate the spectrum of mutations in HT1 in several ethnic groups of the Russian Federation.
Materials and Methods: From 2004 to 2017, 43 patients were diagnosed with HT1. The analysis of amino acids and succinylacetone was performed using NeoGram Amino Acids and Acylcarnitines Tandem Mass Spectrometry Kit and a Sciex QTrap 3200 quadrupole tandem mass spectrometer. Bi-directional DNA sequence analysis was performed on PCR products using an ABI Prism 3500.
Results: In the Russian Federation, the most common mutation associated with HT1 (32.5% of all mutant alleles) is c.1025C>T (p.Pro342Leu), which is typical for the Chechen ethnic group. Patients of the Yakut, the Buryat, and the Nenets origins had a homozygous mutation c.1090G>C (p.Glu364Gln). High frequency of these ethnicity-specific mutations is most likely due to the founder effect. In patients from Central Russia, the splicing site mutations c.554-1G>T and c.1062+5G>A were the most prevalent, which is similar to the data obtained in the Eastern and Central Europe countries.
Conclusion: There are ethnic specificities in the spectrum of mutations in the FAH gene in HT1. The Chechen Republic has one of the highest prevalence of HT1 in the world.
Databáze: MEDLINE
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