Случай множественной экзостозной хондродисплазии в якутской семье, обусловленной редкой мутацией в гене EXT2

Introduction. Multiple osteohondromas (MO) is an autosomal dominant inherited skeletal disease characterized by the formation of multiple cartilaginous exostoses in the areas of growth in a long bones. Difficult issues arise for the genetic counseling of families with MO. We presents the clinical and molecular genetic analysis of four-generation Yakut family with an autosomal dominant inherited MO, caused by a rare mutation in the EXT2 gene. Aim: сonducting a clinical, genealogical, molecular genetic study of patients with a clinical diagnosis MO. Methods. Targeted panel sequencing performed for the 4800 known candidate genes using Trusight One Sequencing Panel (Illumina Inc., USA) on one sample (DNA of proband). Sanger sequencing was performed for validation of candidate disease causing mutation in DNA from a proband and family members. Results. A rare EXT2 nonsense mutation (c.751C> T, p.Gln251*) was revealed by targeted exome sequencing and validated by Sanger sequencing in the 7 MO-affected members of this family. The variant was interpreted as pathogenic based on an in silico analysis. This mutation was absent in 4 healthy members of this family and in 10 controls. Conclusions. This is the first study of EXT2 gene mutation in a Russian patients from Yakut family with MO. Timely health care of patients with diagnosis of MO can contribute to establishment coordinated multispecialty management of the patient focusing on the orthopedic problems issues through childhood.