Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses.
PMID 33632255 | PMCID PMC7905910 | DOI 10.1186/s13023-021-01738-z · Orphanet journal of rare diseases · 2021
BACKGROUND: Hereditary Multiple Exostoses (HME), also known as Multiple Osteochondromas (MO) is a rare genetic disorder characterized by multiple benign cartilaginous bone tumors, which are caused by mutations in the genes for exostosin glycosyltransferase 1 (EXT1) and exostosin glycosyltransferase 2 (EXT2). The genetic defects have not been studied in the Saudi patients. AIM OF STUDY: We investigated mutation spectrum of EXT1 and EXT2 in 22 patients from 17 unrelated families. METHODS: Genomic DNA was extracted from peripheral leucocytes. The coding regions and intron-exon boundaries of both EXT1 and EXT2 genes were screened for mutations by PCR-sequencing analysis. Gross deletions were analyzed by MLPA analysis. RESULTS: EXT1 mutations were detected in 6 families (35%) and 3 were novel mutations: c.739G > T (p. E247*), c.1319delG (p.R440Lfs*4), and c.1786delA (p.S596Afs*25). EXT2 mutations were detected in 7 families (41%) and 3 were novel mutations: c.541delG (p.D181Ifs*89), c.583delG (p.G195Vfs*75), and a gross deletion of approximately 10 kb including promoter and exon 1. Five patients from different families had no family history and carried de novo mutations (29%, 5/17). No EXT1 and EXT2 mutations were found in the remaining four families. In total, EXT1 and EXT2 mutations were found in 77% (13/17) of Saudi HME patients. CONCLUSION: EXT1 and EXT2 mutations contribute significantly to the pathogenesis of HME in the Saudi population. In contrast to high mutation rate in EXT 1 (65%) and low mutation rate in EXT2 (25%) in other populations, the frequency of EXT2 mutations are much higher (41%) and comparable to that of EXT1 among Saudi patients. De novo mutations are also common and the six novel EXT1/EXT2 mutations further expands the mutation spectrum of HME.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | EXT1 | “Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses.” | 0.98 | hgnc_dict_v1 |
| gene | EXT2 | “Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses.” | 0.98 | hgnc_dict_v1 |
| population | Saudi Arabia | “Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses. The genetic defects have not been studied in the Saudi patients. AIM OF STUDY: We investigated mutation spectrum of EXT1 and EXT2 in 22 patients from 17 unrelated families. In total, EXT1 and EXT2 mutations were found in 77% (13/17) of Saudi HME patients. CONCLUSION: EXT1 and EXT2 mutations contribute significantly to the pathogenesis of HME in the Saudi population. In contrast to high mutation rate in EXT 1 (65%) and low mutation rate in EXT2 (25%) in other populations, the frequency of EXT2 mutations are much higher (41%) and comparable to that of EXT1 among Saudi patients.” | 0.95 | saudi_context_rules_v1 |
| variant | c.1319delG | “E247*), c.1319delG (p.R440Lfs*4), and c.1786delA (p.S596Afs*25).” | 0.95 | hgvs_regex_v1 |
| variant | p.R440Lfs | “E247*), c.1319delG (p.R440Lfs*4), and c.1786delA (p.S596Afs*25).” | 0.95 | hgvs_regex_v1 |
| variant | c.1786delA | “E247*), c.1319delG (p.R440Lfs*4), and c.1786delA (p.S596Afs*25).” | 0.95 | hgvs_regex_v1 |
| variant | p.S596Afs | “E247*), c.1319delG (p.R440Lfs*4), and c.1786delA (p.S596Afs*25).” | 0.95 | hgvs_regex_v1 |
| variant | c.541delG | “EXT2 mutations were detected in 7 families (41%) and 3 were novel mutations: c.541delG (p.D181Ifs*89), c.583delG (p.G195Vfs*75), and a gross deletion of approximately 10 kb including promoter and exon 1.” | 0.95 | hgvs_regex_v1 |
| variant | p.D181Ifs | “EXT2 mutations were detected in 7 families (41%) and 3 were novel mutations: c.541delG (p.D181Ifs*89), c.583delG (p.G195Vfs*75), and a gross deletion of approximately 10 kb including promoter and exon 1.” | 0.95 | hgvs_regex_v1 |
| variant | c.583delG | “EXT2 mutations were detected in 7 families (41%) and 3 were novel mutations: c.541delG (p.D181Ifs*89), c.583delG (p.G195Vfs*75), and a gross deletion of approximately 10 kb including promoter and exon 1.” | 0.95 | hgvs_regex_v1 |
| variant | p.G195Vfs | “EXT2 mutations were detected in 7 families (41%) and 3 were novel mutations: c.541delG (p.D181Ifs*89), c.583delG (p.G195Vfs*75), and a gross deletion of approximately 10 kb including promoter and exon 1.” | 0.95 | hgvs_regex_v1 |