An extension of the admixture test for the study of genetic heterogeneity in hereditary multiple exostoses.
ABSTRACT Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the presence of multiple cartilage-capped exostoses in the juxta-epiphyseal regions of the long bones. EXT is heterogeneous with at least three different locations currently having been identified on chromosomes 8, 11 and 19. We have tested a series of 29 EXT families for possible linkage to the three disease loci and estimated the probability of linkage of the disease to each locus in our series, by using an extension of the admixture test, which makes modelling of heterogeneous monogenic disease feasible. The maximum likelihood was obtained for proportions of 44%, 28% and 28% of families being linked to chromosome 8, 11 and 19, respectively. The a posteriori probability of linkage of the disease to EXT1, EXT2 and EXT3 was greater than 80% for 8/29, 5/29 and 3/29 families, respectively, and did not give evidence of a fourth locus for the disease. The present approach can be generalized to the investigation of genetic heterogeneity in other monogenic diseases, as it simultaneously estimates the location of each disease gene and the proportion of families linked to each locus.
Article: A hereditary multiple exostoses patient suffering multi-fractures: Report of the case and contemporary approach to disease’s aetiology.[show abstract] [hide abstract]
ABSTRACT: Case report: It is reported a 37 year old patient, with a history of hereditary multiple exostoses, suffered bilateral supracondylar femur fractures and a fracture of the left tibia, due to a road traffic accident. He was treated using the Ilizarov apparatus. The surgical technique is described. Results: The patient was followed up for 19 months after the surgery. The fractures of the right femur and left tibia healed sufficiently and the Ilizarov apparatus was removed 9 months from surgery. The fracture of the left femur took longer to heal completely and therefore the Ilizarov apparatus was removed 19 months from surgery. Discussion: The contemporary view on the aetiology of HME is presented and the usefulness of the Ilizarov apparatus in treating fractures in HME patients is discussed.Acta Orthopaedica et Traumatologica Hellenica. 01/2012; 63(1):47 - 52.
Article: Multiple osteochondromas: clinicopathological and genetic spectrum and suggestions for clinical management.[show abstract] [hide abstract]
ABSTRACT: Multiple Osteochondromas is an autosomal dominant disorder characterised by the presence of multiple osteochondromas and a variety of orthopaedic deformities. Two genes causative of Multiple Osteochondromas, Exostosin-1 (EXT1) and Exostosin-2 (EXT2), have been identified, which act as tumour suppressor genes. Osteochondroma can progress towards its malignant counterpart, secondary peripheral chondrosarcoma and therefore adequate follow-up of Multiple Osteochondroma patients is important in order to detect malignant transformation early.This review summarizes the considerable recent basic scientific and clinical understanding resulting in a multi-step genetic model for peripheral cartilaginous tumorigenesis. This enabled us to suggest guidelines for clinical management of Multiple Osteochondroma patients. When a patient is suspected to have Multiple Osteochondroma, the radiologic documentation, histology and patient history have to be carefully reviewed, preferably by experts and if indicated for Multiple Osteochondromas, peripheral blood of the patient can be screened for germline mutations in either EXT1 or EXT2. After the Multiple Osteochondroma diagnosis is established and all tumours are identified, a regular follow-up including plain radiographs and base-line bone scan are recommended.Hereditary Cancer in Clinical Practice 01/2004; 2(4):161-73. · 1.68 Impact Factor