Genetic analysis of seven pateints with Hereditary Multiple Osteochondromas (HMO).

Background: HMO (Hereditary Multiple Osteochondroma), an uncommon autosomal dominant disorder, is characterized by the development of multiple osteochondromas, which are nonmalignant cartilage-capped bone tumors growing outwards from long bone metaphyses.

Methods: The present work retrospectively analyzed seven children with HMO who were enrolled for routine clinical diagnosis and treatment, including X-ray examination. Subsequent genetic detection was carried out using whole exome sequencing (WES). In addition, this work applied Sanger sequencing to be the validation approach. Moreover, this work also examined amino acid (AA) evolutionary conservatism under the influence of certain missense variants.

Results: The clinical indications of all seven patients and their family members were thoroughly indexed. WES identified diagnostic variants in the or gene in these patients. In these variants, four were reported for the first time, namely : c.1285-2A>T, : c.1139delT, : c.203G>A, and : c.1645_1673del. Familial validation revealed that three of the variants were hereditary, while the other four were , which was consistent with the phenotype in each case.

Conclusion: Our results expanded HMO variation spectrum, and laid certain foundations for the precise counseling of those affected families.