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New Mutations of EXT1 and EXT2 Genes in German Patients with Multiple Osteochondromas
Author(s) -
Heinritz Wolfram,
Hüffmeier Ulrike,
Strenge Sibylle,
Miterski Bianca,
Zweier Christiane,
Leinung Steffen,
Bohring Axel,
Mitulla Beate,
Peters Usha,
Froster Ursula G.
Publication year - 2009
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2009.00508.x
Subject(s) - genetics , gene , exon , splice , biology , mutation , rna splicing , microbiology and biotechnology , rna
Summary 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 d enaturing h igh p erformance l iquid c hromatography (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 .