Mutational Analysis of EXT1 in a Chinese Family Affected by Hereditary Multiple Osteochondroma

Guangzhi Yuan; Qiang Su; Wenjun Liao; Wei Hou; Linke Huang; Peng Wang; Huayu Wu

doi:10.1155/2021/8888948

Mutational Analysis of EXT1 in a Chinese Family Affected by Hereditary Multiple Osteochondroma

Biomed Res Int. 2021 Aug 6:2021:8888948. doi: 10.1155/2021/8888948. eCollection 2021.

Authors

Guangzhi Yuan¹, Qiang Su², Wenjun Liao³, Wei Hou⁴, Linke Huang¹, Peng Wang⁵, Huayu Wu⁴

Affiliations

¹ Orthopedics Department, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
² Guangxi Institute for Food and Drug Control, Guangxi, China.
³ Department of Cell Biology and Genetics, Guangxi Medical University, Nanning, Guangxi, China.
⁴ Department of Physical Examination/Health Management Department, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
⁵ Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China.

Abstract

Objectives: To discuss the mutational features and their relationships with disease in a family with hereditary multiple osteochondroma (HMO) from Guangxi Province (GXBB-1 family), China.

Methods: Genomic DNA and total mRNA were extracted from peripheral blood cells of GXBB-1 family members. Whole elements of the EXT1gene and its transcript, including exons, introns, exon-intron boundaries, and coding sequence (CDS) clones, were amplified and sequenced. Allele-specific PCR was used to confirm the position and type of mutation.

Results: All patients from the GXBB-1 family harbored the cosegregating heterozygous c.1056+1G>A mutation located in EXT1at an exon-intron boundary. Another three single-nucleotide polymorphisms (SNPs) were also detected in the patients, including IVS2+1G>A in intron 2, c.1844 T>C [p.Pro (CCT) 614Pro (CCC)] in exon 3, and c.2534G>A [p.Glu (GAG) 844Glu (GAA)] in exon 9. The latter two SNPs were synonymous variations.

Conclusions: The heterozygous c.1056+1G>A mutation cosegregated with the phenotype, indicating that it is a pathogenic mutation in the GXBB-1 family. This mutation is reported for the first time in Chinese HMO patients. IVS2+1G>A and c.2534G>A have no relationship with the occurrence of disease. However, c.1844 T>C and c.1056+1G>A are linked, and their interaction needs to be further studied. c.1844T>C is a new SNP that has not been reported internationally.

MeSH terms

Asian People / genetics*
China
DNA Mutational Analysis / methods*
Exostoses, Multiple Hereditary / genetics*
Female
Humans
Male
Mutation
N-Acetylglucosaminyltransferases / genetics*
Pedigree
Polymorphism, Single Nucleotide
Sequence Analysis, DNA

Substances

N-Acetylglucosaminyltransferases
exostosin-1