title: Novel and recurrent mutations in the EXT1 and EXT2 genes in Chinese kindreds with multiple osteochondromas.
abstract: Multiple osteochondromas (MO) is an autosomal dominant hereditary disorder caused by heterozygous germline mutations in the exostonsin-1 (EXT1) or exostosin-2 (EXT2) genes. In this study, we screened mutations in the EXT1/EXT2 genes in four Chinese MO kindreds by direct sequencing. Three point mutations were detected, including a nonsense mutation in the EXT2 gene (c.544C > T) and two splice site mutations in the EXT1 and EXT2 genes, respectively (EXT1: c.1883 + 1G > A and EXT2: c.1173 + 1G > T). Although splice site mutations constitute at least 10% of all mutations that cause MO, there has been limited research on their pathogenic effect on RNA processing due to poor availability of patient RNA samples. In this study, ex vivo and in vivo splicing assays were used to investigate the effect of EXT1 and EXT2 mutations on aberrant splicing at the mRNA level. Our results indicate that identified splice site mutations can cause either cryptic splice site usage or exon skipping.
authors: The Research Center for Medical Genomics, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, 110001, China.
authors: Yuhong
authors: Y
authors: Wu
authors: Xuesha
authors: X
authors: Xing
authors: Shaonian
authors: S
authors: Xu
authors: Hongwei
authors: H
authors: Ma
authors: Lihua
authors: L
authors: Cao
authors: Shusen
authors: S
authors: Wang
authors: Yang
authors: Y
authors: Luo
mesh_terms: D000328:Adult; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D001483:Base Sequence; D001859:Bone Neoplasms / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D002648:Child; D002681:China / Q000208:ethnology; D004252:DNA Mutational Analysis; D005097:Exostoses, Multiple Hereditary / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D005192:Family Health / Q000208:ethnology*; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites; D055815:Young Adult; D000099065:Exostosin 2; D000099058:Exostosin 1
chemical_list: D022821:RNA Splice Sites; D017351:N-Acetylglucosaminyltransferases; D000099058:Exostosin 1; D000099065:Exostosin 2
keywords: EXT1; EXT2; ex vivo splicing assay; mRNA; multiple osteochondromas