Corelaţia între manifestarea fenotipică, tipul mutaţiei şi varianta alelică a genelor ciclului folat la pacienţii cu distrofia musculară duchenne/becker

Abstract

The correlation between phenotypic manifestations, type of mutation and alelic variants of the genes of folate cycle in patients with Duchenne/Becker muscular distrophy The frequency of different alelic variants of MTHFR gene in patients with DMD/B was estimated during this investigation. The incidence of C677T allelic variant in patients with DMD/B was 21,4%. This mutation leads to reduction of activity of MTHFR by 35-60%, and, consequently, leads to a reduced level of methionine, which influences the myopathyc process. Analysis of MTRR polymorphism revealed the prevalence of A66G (92,9%), which leads to 4- times lower activity of this enzyme. Patients with in-frame deletions in dystrophin gene in combination with heterozygous status MTHFR, MTRR genes have severe clinical picture instead the mild one. Patients with mild clinical picture have the next genotype of folate cycle genes: 677-TT, 1298- CC.

A fost estimată incidenţa diferitelor variante alelice ale genei MTHFR la pacienţii cu DMD/B. Incidenţa variantei alelice C677T la pacienţi cu DMD/B constituie 21,4%. Substituţia dată determină micşorarea cantităţii de metionină, ceea ce influenţează procesul miopatic. Analiza polimorfismului genei MTRR a arătat prevalarea variantei alelice A66G (92,9%), cea ce conduce la micşorarea activităţii acestei enzime de 4 ori. La bolnavii cu deleţii in-frame în gena distrofinei în combinaţie cu starea heterozigotă după genele MTHFR, MTRR în locul tabloului clinic uşor se observă tabloul clinic grav. La bolnavi cu clinica uşoară a fost depistat polimorfismul genelor ciclului folat - 677-TT, 1298-CC.