Hereditary Multiple Exostoses: Clinical, Molecular and Radiologic Survey in 9 Families
| Autor: | Kuklík M, Kučerová Vidrová, Tomas Honzik, Chomiak J, Hana Hansikova, Jiri Zeman, Švecová Š, Medek K, Markéta Tesařová, Kamila Berankova |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proband Adult Male Pediatrics medicine.medical_specialty Adolescent Hereditary multiple exostoses Nonsense mutation lcsh:Medicine Gene mutation N-Acetylglucosaminyltransferases Short stature 03 medical and health sciences symbols.namesake Young Adult Medicine Humans Multiplex ligation-dependent probe amplification Child Exostosis Aged Czech Republic Sanger sequencing lcsh:R5-920 business.industry Multiple exostoses lcsh:R EXT2 General Medicine Sequence Analysis DNA EXT1 Middle Aged medicine.disease 030104 developmental biology Child Preschool Mutation symbols Female medicine.symptom lcsh:Medicine (General) business Exostoses Multiple Hereditary |
| Zdroj: | Prague Medical Report, Vol 118, Iss 2, Pp 87-94 (2017) |
| ISSN: | 1214-6994 |
| Popis: | Hereditary multiple exostoses (HME) represents a heterogeneous group of diseases often associated with progressive skeletal deformities. Most frequently, mutations inEXT1andEXT2genes with autosomal dominant inheritance are responsible for HME. In our group of 9 families with HME we evaluated the clinical course of the disease and analysed molecular background using Sanger sequencing and MLPA inEXT1andEXT2genes. The mean age in our group of patients, when the first exostosis was recognised was 4.5 years (range 2–10 years) and the number of exostoses per one patient documented on X-ray ranged from 2 to 54. Most of the exostoses developed before the growth was completed and they were dominantly localised in the distal femurs, proximal tibia, proximal humerus and distal radius. In all patients, at least one to 8 surgeries were necessary due to complaints and local complications, but neither patient developed malignant transformation. In half of the patients, the disease resulted in short stature. DNA analyses were positive in 7 families. In five probands, differentEXT1gene mutations resulting in premature stop-codon (p.Gly124Argfs*65, p.Leu191*, p.Trp364Lysfs*11, p.Val371Glyfs*10, p.Leu490Profs*31) were found. In two probands, nonsense mutations were found inEXT2gene (p.Val187Profs*115, p.Cys319fs*46). Five mutations have been novel and two mutations have occurredde novoin probands. Although the risk for malignant transformation is usually low, especially in patients with low number of exostoses, early diagnostics and longitudinal follow up of patients is of a big importance, because early surgery can prevent progression of secondary bone deformities. |
| Databáze: | OpenAIRE |
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