Mutation analysis and prenatal diagnosis of EXT1 gene mutations in Chinese patients with multiple osteochondromas. 2011

Hai-Yan Zhu, and Ya-Li Hu, and Ying Yang, and Xing Wu, and Rui-Fang Zhu, and Xiang-Yu Zhu, and Hong-Lei Duan, and Ying Zhang, and Jin-Yong Zhou
Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, the Affiliated Drum Tower Hospital of Nanjing University School of Medicine, Nanjing, Jiangsu 210008, China.

BACKGROUND Multiple osteochondromas (MO), an inherited autosomal dominant disorder, is characterized by the presence of multiple exostoses on the long bones. MO is caused by mutations in the EXT1 or EXT2 genes which encode glycosyltransferases implicated in heparin sulfate biosynthesis. METHODS In this study, efforts were made to identify the underlying disease-causing mutations in patients from two MO families in China. RESULTS Two novel EXT1 gene mutations were identified and no mutation was found in EXT2 gene. The mutation c.497T > A in exon 1 of the EXT1 gene was cosegregated with the disease phenotype in family 1 and formed a stop codon at amino acid site 166. The fetus of the proband was diagnosed negative. In family 2, the mutation c.1430-1431delCC in exon 6 of the EXT1 gene would cause frameshift and introduce a premature stop codon after the reading frame being open for 42 amino acids. The fetus of this family inherited this mutation from the father. CONCLUSIONS Mutation analysis of two MO families in this study demonstrates its further application in MO genetic counseling and prenatal diagnosis.

UI MeSH Term Description Entries
D008297 Male Males
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D005097 Exostoses, Multiple Hereditary Hereditary disorder transmitted by an autosomal dominant gene and characterized by multiple exostoses (multiple osteochondromas) near the ends of long bones. The genetic abnormality results in a defect in the osteoclastic activity at the metaphyseal ends of the bone during the remodeling process in childhood or early adolescence. The metaphyses develop benign, bony outgrowths often capped by cartilage. A small number undergo neoplastic transformation. Chondrodysplasia, Hereditary Deforming,Diaphyseal Aclasis,Exostoses, Familial,Exostoses, Hereditary Multiple,Exostoses, Multiple,Exostoses, Multiple Cartilaginous,Hereditary Multiple Exostoses,Osteochondromas, Multiple,Bessel-Hagen Disease,Exostoses, Multiple, Type I,Exostosis, Familial,Exostosis, Hereditary Multiple,Exostosis, Multiple,Exostosis, Multiple Cartilaginous,Familial Exostoses,Hereditary Multiple Exostosis,Multiple Cartilaginous Exostoses,Multiple Hereditary Exostoses,Multiple Osteochondromas,Multiple Osteochondromatosis,Aclases, Diaphyseal,Aclasis, Diaphyseal,Cartilaginous Exostoses, Multiple,Cartilaginous Exostosis, Multiple,Chondrodysplasias, Hereditary Deforming,Deforming Chondrodysplasia, Hereditary,Deforming Chondrodysplasias, Hereditary,Diaphyseal Aclases,Familial Exostosis,Hereditary Deforming Chondrodysplasia,Hereditary Deforming Chondrodysplasias,Hereditary Exostoses, Multiple,Multiple Cartilaginous Exostosis,Multiple Exostoses,Multiple Exostoses, Hereditary,Multiple Exostosis,Multiple Exostosis, Hereditary,Multiple Osteochondroma,Osteochondroma, Multiple
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D017351 N-Acetylglucosaminyltransferases Enzymes that catalyze the transfer of N-acetylglucosamine from a nucleoside diphosphate N-acetylglucosamine to an acceptor molecule which is frequently another carbohydrate. EC 2.4.1.-. N-Acetylglucosamine Transferases,N Acetylglucosamine Transferases,N Acetylglucosaminyltransferases,Transferases, N-Acetylglucosamine
D044466 Asian People Persons having origins in any of the Asian racial groups of the Far East, Southeast Asia, or the Indian subcontinent including, for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and Vietnam. Note that OMB category ASIAN is available for United States population groups. Race and ethnicity terms, as used in the federal government, are self-identified social construct and may include terms outdated and offensive in MeSH to assist users who are interested in retrieving comprehensive search results for studies such as in longitudinal studies. Asian Continental Ancestry Group,Asian Person,Asiatic Race,Mongoloid Race,Asian Peoples,Asian Persons,Asiatic Races,Mongoloid Races,People, Asian,Person, Asian,Race, Asiatic,Race, Mongoloid

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