Novel EXT1 and EXT2 mutations in hereditary multiple exostoses families of Indian origin.

BACKGROUND: Hereditary multiple exostosis (HME) is an autosomal dominant bone disorder, characterized by short stature and the presence of multiple benign tumors mainly at the ends of long bones. HME is genetically heterogeneous with two known genes on 8q24 (EXT1) and 11p11 (EXT2), and a third minor locus mapped to 19p (EXT3). The majority of EXT1 and EXT2 mutations result in premature protein truncation and loss of function. MATERIALS AND METHODS: We analyzed two autosomal dominant HME families of Indian origin. Linkage analysis using fluorescently labeled microsatellite markers at the candidate gene regions was performed. Mutation analysis was carried out by bidirectional sequencing of purified PCR products. RESULTS: We found linkage in one family to EXT1 and in the other family to EXT2. Mutation screening in the EXT1 gene revealed a novel frameshift mutation, a single base deletion in exon 1 (c.142delC). This mutation segregated in all affected members and was absent in the unaffected family members and 60 unrelated controls. In the second family, a previously unreported stop mutation, the substitution c.817C>T, was observed in the EXT2 gene in all affected members and in none of the unaffected family members and 90 unrelated controls. CONCLUSIONS: Our findings expand the mutation spectrum of EXT1 and EXT2 and highlight the genetic and phenotypic heterogeneity of HME.

Neglected fractured neck of the femur: a predictive classification and treatment by osteosynthesis.

A prospective study of 236 patients with neglected femoral neck fractures was done to determine the usefulness of a preoperative classification based on the radiologic changes that occur at the site of the fracture. Thirty-four patients were observed in Group I, 125 patients were observed in Group II, and nine patients were observed in Group III. One-hundred sixty-eight patients (71.2%) were treated by closed reduction and internal fixation with cancellous screw and free fibular graft. The fracture union was achieved in all 34 patients of Group I. Union was achieved in 111 (88.8%) of 125 patients in Group II, and it was achieved in three (33.3%) of nine patients in Group III. In 143 (96.6%) of 148 successfully treated patients, the hip joint remained clinically asymptomatic with normal radiological union. One-way analysis of variance showed a good predictive value of the above classification with the results achieved by osteosynthesis. A good interobserver agreement also was seen in all three groups. We concluded that the classification is of use in the preoperative evaluation of neglected fractures of the neck of femur. For a successful osteosynthesis, the femoral head should be viable, with the size of the proximal fragment at least 2.5 cm long.