title: New mutations of EXT1 and EXT2 genes in German patients with Multiple Osteochondromas.
abstract: Mutations in either the EXT1 or EXT2 genes lead to Multiple Osteochondromas (MO), an autosomal dominantly inherited disorder. This is a report on clinical findings and results of molecular analyses of both genes in 23 German patients affected by MO. Mutation screening was performed by using denaturing high performance liquid chromatography (dHPLC) and automated sequencing. In 17 of 23 patients novel pathogenic mutations have been identified; eleven in the EXT1 and six in the EXT2 gene. Five patients were carriers of recurrent mutations in the EXT2 gene (p.Asp227Asn, p.Gln172X, p.Gln258X) and one patient had no detectable mutation. To demonstrate their pathogenic effect on transcription, two complex mutations in EXT1 and EXT2 and three splice site mutations were characterized by mRNA investigations. The results obtained provide evidence for different aberrant splice effects - usage of new cryptic splice sites and exon skipping. Our study extends the mutational spectrum and understanding of pathogenic effects of mutations in EXT1 and EXT2.
authors.affiliation: Institute of Human Genetics, Medical Faculty at the University of Leipzig, Leipzig, Germany. reichsi@medizin.uni-leipzig.de
authors.forename: Wolfram
authors.initials: W
authors.lastname: Heinritz
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hüffmeier
authors.forename: Sibylle
authors.initials: S
authors.lastname: Strenge
authors.forename: Bianca
authors.initials: B
authors.lastname: Miterski
authors.forename: Christiane
authors.initials: C
authors.lastname: Zweier
authors.forename: Steffen
authors.initials: S
authors.lastname: Leinung
authors.forename: Axel
authors.initials: A
authors.lastname: Bohring
authors.forename: Beate
authors.initials: B
authors.lastname: Mitulla
authors.forename: Usha
authors.initials: U
authors.lastname: Peters
authors.forename: Ursula G
authors.initials: UG
authors.lastname: Froster