Clinical and molecular studies of EXT1/EXT2 in Bulgaria

Abstract

EXT1/EXT2-CDG (Multiple cartilagineous exostoses, hereditary multiple osteochondroma (MO); OMIM 133700/133701) are common defects of O-xylosylglycan glycosylation. The diagnostic criteria are at least two osteochondromas of the juxta-epiphyseal region of long bones with in the majority of cases a positive family history and/or mutation in one of the EXT genes. The authors report data on clinical symptoms and complications of 23 patients (from 16 families), discussing the family history, age of diagnosis, new clinical and molecular data. Fifteen mutations and large deletions, of which nine are new, were detected in the EXT1 and EXT2 gene by sequence analysis, FISH and MLPA analysis.

A broad spectrum of genomic changes in latinamerican patients with EXT1/EXT2-CDG

“…Nevertheless, no family history for MO was reported in 56% of MO patients. Patients with a mutation in the EXT2 gene showed a smaller number of affected bones (data not shown) consistent with a recent study39. The most frequently observed skeletal deformations in our patients were shortening of limbs, varus or valgus knee, short metacarpal bones, scoliosis, shortened stature and synostosis, with no evidence of differences between the grade of severity in the phenotype observed in patients with EXT1 or EXT2 (Figure 1).…”

Old gene, new phenotype: mutations in heparan sulfate synthesis enzyme, EXT2 leads to seizure and developmental disorder, no exostoses

“…To the best of our knowledge, there have not been any reports of autosomal-recessive HME. Interestingly, there has only been one report of HME and seizures in a patient with a mutation in EXT2 29. There have been multiple reports of patients with multiple exostoses, intellectual disability and seizures, diagnosed with Potocki–Shaffer syndrome (OMIM 601224), a rare contiguous gene deletion syndrome due to haploinsufficiency of the 11p11.2 region, encompassing EXT2 30 31.…”

Multiple Hereditary Exostoses: Report of an EXT2 Gene Mutation in a Colombian Family

“…The ratio between females/males is 1.5:1. 3,7 OCs are the most frequent benign tumors of the bones, and nearly 80% manifest in the first 10 years of life due to chondrocyte proliferation and bone growth in the metaphyseal region in children. 8,9 MHE is caused by pathogenic variants in the EXT gene family that encode for exostosin proteins (EXT).…”

“…11 Diagnostic criteria include at least two OC in the juxtaepiphyseal region of the long bones with a family history of MHE and/or a mutation in one of the EXT genes. 5,7 Molecular diagnosis must be made of the EXT1 or EXT2 gene mutation to confirm the mutation and to assess the degree of phenotype/genotype relationship. Differential diagnoses to be ruled out include Ollier's disease, chondrosarcomas, multiple epiphyseal dysplasia, and periosteal chondroma.…”