Особенности спектра мутаций при болезни Краббе в Российской Федерации

Krabbe’s disease (KD) is a rare inherited autosomal recessive lysosomal storage disease. KD is caused by mutations in the GALC gene leading to deficiency of galactosylceramidase. KD oссurs in 1 per 100 000 newborns, although some countries have a higher incidence rate. The exact KD incidence in Russia is unknown. A major mutation leading to the KD development is a large deletion affecting exons 11-17 of the GALC gene с.1161+6532_polyA+9kbdel (IVS10del30kb). This mutation occurs in 50% of KD cases in the European population. Patients from different regions were studied to analyze the mutation spectrum and the incidence in the Russian population. The incidence rate of the large deletion in our study equals 54%, that is comparable with European population. However, in the Chechen Republic this mutation is much more common than in other regions. 950 samples were studied, 7 heterozygous carriers of frequent mutation were identified. Thus, the estimated KD incidence rate is 1:51237 considering other mutations, and it is higher than that in the European population. Additional analysis of all detected GALC mutations revealed a genetic variant c.578T>C, p.Ile193Thr with allelic frequency measured up 8%. This substitution was described in our selection for the first time and presented only in Russian patients with late infantile form of the disease.