Hu Zheng-mao, Zheng Duo, Pan Qian, Yang Yi-feng, Zhao Tian-li, Liu Xiao-ping, Wu Ling-qian, Jiang Dong-gui, Xia Kun, Xia Jia-hui
National Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan, 410078 PR China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2004 Apr;21(2):97-100.
To identify the gene causing hereditary multiple exostoses in a Chinese pedigree.
Linkage analysis was carried out in the family using microsatellite markers on chromosome 8, 11 and 19 respectively. To detect the mutation, the whole coding sequence and the intron-exon boundaries of the candidate gene were amplified and sequenced. The reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to amplify the mutated mRNA.
The disease-causing gene of the family was linked to the EXT2 locus on chromosome 11. A mutation IVS2+1G>A was detected in EXT2 and resulting in 221 bp deletion from 316 to 536 of coding sequence(CDS), which was co-segregated with the disease phenotype. This change led to deletion from codon 106 to codon 178 and subsequent 2 nucleotides, producing a frameshift and truncated protein of 125 aa.
The mutation IVS2+1G>A is the disease-causing mutation in the Chinese pedigree with hereditary multiple exostoses.
鉴定一个中国家系中导致遗传性多发性骨软骨瘤的基因。
分别使用位于8号、11号和19号染色体上的微卫星标记对该家系进行连锁分析。为检测突变，对候选基因的整个编码序列和内含子-外显子边界进行扩增和测序。进行逆转录聚合酶链反应（RT-PCR）以扩增突变的mRNA。
该家系的致病基因与11号染色体上的EXT2位点连锁。在EXT2基因中检测到一个IVS2+1G>A突变，导致编码序列（CDS）从316位到536位缺失221 bp，该突变与疾病表型共分离。这种变化导致从第106密码子到第178密码子以及随后的2个核苷酸缺失，产生移码并截短为125个氨基酸的蛋白质。
IVS2+1G>A突变是该遗传性多发性骨软骨瘤中国家系的致病突变。
