Alkaptonuria in Russia: mutational spectrum and novel variants

Eur J Med Genet. 2021 Feb 20:104165. doi: 10.1016/j.ejmg.2021.104165. Online ahead of print.ABSTRACTAlkaptonuria is a rare genetic disease caused by mutations in HGD gene. Here we report the results of genetic and biochemical analysis of 49 Russian patients with alkaptonuria. One of the common variants c.481G>A; p.(Gly161Arg) comprising 72.4% of identified alleles was found in 45 of 49 patients in our cohort, which is probably the highest frequency of this variant worldwide. 9 novel variants were found: 8 missense, 2 splicing and 1 loss of start-codon. For missense variants we performed bioinformatic analysis, protein 3D-modeling and molecular dynamics simulations, which strongly suggest their pathogenic effect. For the rare synonymous variant c.753C>T; p.(Gly251Gly), which was found in 3 cases and predicted to activate cryptic splice site, we performed the detailed functional analysis on patient`s cDNA and minigene assay and confirmed its pathogenicity.PMID:33621656 | DOI:10.1016/j.ejmg.2021.104165

Source: European Journal of Medical Genetics - February 23, 2021 Category: Genetics & Stem Cells Authors: Igor Bychkov Elena Kamenets Marina Kurkina Georgiy Rychkov Alexandra Ilyushkina Aleksandra Filatova Darya Guseva Galina Baydakova Andrey Nekrasov Aleksandr Cheblokov Mikhail Skoblov Ekaterina Zakharova Source Type: research