Disease relevance of Exostoses, Multiple Hereditary

• It maps proximal of EXT1, which is affected in a subgroup of patients with multiple cartilaginous exostoses and deleted in all patients with TRPS type II (TRPS II, or Langer-Giedion syndrome, MIM 150230; ref.2-5) [1].
• Discordant segregation between COL2A1 and the mutant locus was seen in pedigrees with multiple epiphyseal dysplasia, autosomal recessive spondyloepiphyseal dysplasia tarda, hypochondroplasia, pseudoachondroplasia, diaphyseal aclasis, and trichorhinophalangeal syndrome [2].
• Novel mutations in the EXT1 gene in two consanguineous families affected with multiple hereditary exostoses (familial osteochondromatosis) [3].
• Germline mutation and functional loss of EXT1 or EXT2 are commonly found in multiple osteochondromas and predispose to the development of chondrosarcoma [4].

Psychiatry related information on Exostoses, Multiple Hereditary

• Pertinent features include a bulbous nose, sparse hair, protruding ears, multiple cartilaginous exostoses, cone-shaped phalangeal epiphyses, short stature, microcephaly, and mental retardation [5].

High impact information on Exostoses, Multiple Hereditary

• The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes [6].
• Hereditary multiple exostoses (HME), a dominantly inherited genetic disorder characterized by multiple cartilaginous tumors, is caused by mutations in members of the EXT gene family, EXT1 or EXT2 [7].
• It combines the clinical features of TRPS I and multiple cartilaginous exostoses (EXT) [8].
• Multiple hereditary exostoses (HME) is an autosomal dominant developmental disorder exhibiting multiple osteocartilaginous bone tumors that generally arise near the ends of growing long bones [3].
• Osteochondroma most frequently arises sporadically and as a solitary lesion, but may also arise as multiple lesions characterizing the autosomal dominant disorder hereditary multiple exostoses (HME) and the contiguous gene-deletion syndrome, Langer-Giedion syndrome (LGS) [9].

Biological context of Exostoses, Multiple Hereditary

• The EXT family of putative tumor suppressor genes affect endochondral bone growth, and mutations in EXT1 and EXT2 genes cause the autosomal dominant disorder Hereditary Multiple Exostoses (HME) [10].

Gene context of Exostoses, Multiple Hereditary

• Exogenous administration of TGFbeta1 to cultures of hereditary multiple exostosis eliminates FGF9 expression [11].
• Hereditary multiple exostoses (HME), an autosomal skeletal disorder characterized by cartilage-capped excrescences, has been ascribed to mutations in EXT 1 and EXT 2, two tumor suppressor-related genes encoding glycosyltransferases involved in the heparan sulfate proteoglycan (HSPG) biosynthesis [12].
• Otosclerosis in multiple exostosis [13].
• We report a 50-year-old male patient with hereditary multiple exostoses (HME) and ankylosing spondylitis (AS) [14].
• Picture of the month. Hereditary multiple exostoses (diaphyseal aclasis) [15].

Analytical, diagnostic and therapeutic context of Exostoses, Multiple Hereditary

• Mutation screening of EXT1 and EXT2 by direct sequence analysis and MLPA in patients with multiple osteochondromas: splice site mutations and exonic deletions account for more than half of the mutations [16].

References