Hereditary multiple and isolated sporadic exostoses in the same kindred : identification of the causative gene (EXT2) and detection of a new mutation, nt112delAT, that distinguishes the two phenotypes.

• Hereditary multiple exostoses (HME) is a well known autosomal dominant hereditary orthopedic disorder. Isolated exostoses, on the other hand, occur as sporadic events or as secondary post-traumatic sequel. The occurrence of solitary exostoses in individuals from pedigrees affected with HME may distort conclusions about carrier status and/or diagnosis. Both conditions are potentially malignant and both are associated with genetic alterations in either EXT1 or EXT2 genes. In this study, we present a seven-generation family from western Sweden consisting of 170 blood relatives, 38 of whom had multiple cartilaginous exostoses, while 8 had isolated exostoses. Linkage analysis aimed to discern one of the known EXT genes demonstrated linkage of the HME phenotype to the EXT2 gene. Subsequent mutation analysis revealed a novel mutation, nt112delAT, in this gene. All carriers of the detected mutation had multiple exostoses, indicating full penetrance. None of the pedigree members with isolated exostoses were carriers of the detected mutation. Two of the mutation carriers developed chondrosarcoma yielding a 5.2% risk of malignant development for this mutation. The detection of this mutation has enabled us to provide appropriate genetic counseling concerning this complex situation.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

exostosin 2

exostosin-2

n acetylglucosaminyltransferase

aged

article

chromosome analysis

DNA sequence

female

gene deletion

genetics

hereditary multiple exostosis

human

male

middle aged

neoplasm

pathophysiology

pedigree

Cytogenetic Analysis

Exostoses

Multiple Hereditary

Humans

N-Acetylglucosaminyltransferases

Neoplasms

Sequence Analysis

DNA

Sequence Deletion

Aged

Cytogenetic Analysis

Exostoses

Multiple Hereditary

genetics

physiopathology

Female

Humans

Male

Middle Aged

N-Acetylglucosaminyltransferases

Neoplasms

Pedigree

Sequence Analysis

DNA

Sequence Deletion

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)