Large-scale mutational analysis in the EXT1 and EXT2 genes for Japanese patients with multiple osteochondromas.
Large-scale mutational analysis in the EXT1 and EXT2 genes for Japanese patients with multiple osteochondromas.
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DOI：
10.1186/s12863-016-0359-4
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发表时间：
2016-03-09
期刊：
影响因子：
2.9
通讯作者：
Matsumoto K
中科院分区：
文献类型：
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作者：
Ishimaru D;Gotoh M;Takayama S;Kosaki R;Matsumoto Y;Narimatsu H;Sato T;Kimata K;Akiyama H;Shimizu K;Matsumoto K
多发性骨软骨瘤（multiple osteochondroma，MO）是一种以多发性骨软骨瘤形成为特征的常染色体显性遗传性骨骼疾病，外生骨素-1（exostosin-1，EXT 1）和外生骨素-2（exostosin-2，EXT 2）是MO的主要致病基因。在这项研究中，我们评估了日本MO家族的遗传背景和突变模式。我们评估了71个MO家族的112例患者。从外周血白细胞中分离基因组DNA。PCR扩增后直接测序EXT 1和EXT 2的外显子和外显子/内含子连接。47个MO家系中有52个突变发生在EXT 1或EXT 2基因上，其中42.3%（22/52）的突变为新突变。29个家庭（40.8%）存在EXT 1突变，15个家庭（21.1%）存在EXT 2突变。有趣的是，三个家庭（4.2%）在EXT 1和EXT 2中都有突变。24个家族（33.8%）没有表现出EXT 1或EXT 2突变。关于鉴定的突变类型，59.6%的突变为失活突变，38.5%的突变为错义突变。我们发现，在日本MO家族中，EXT 1突变的患病率高于EXT 2突变。此外，我们在这个日本MO队列中发现了22个新的EXT 1和EXT 2突变。本研究反映了MO基因型的多样性。本文的在线版本（doi：10.1186/s12863-016-0359-4）包含补充材料，可供授权用户使用。
Multiple osteochondroma (MO) is an autosomal dominant skeletal disorder characterized by the formation of multiple osteochondromas, and exostosin-1 (EXT1) and exostosin-2 (EXT2) are major causative genes in MO. In this study, we evaluated the genetic backgrounds and mutational patterns in Japanese families with MO. We evaluated 112 patients in 71 families with MO. Genomic DNA was isolated from peripheral blood leucocytes. The exons and exon/intron junctions of EXT1 and EXT2 were directly sequenced after PCR amplification. Fifty-two mutations in 47 families with MO in either EXT1 or EXT2, and 42.3 % (22/52) of mutations were novel mutations. Twenty-nine families (40.8 %) had mutations in EXT1, and 15 families (21.1 %) had mutations in EXT2. Interestingly, three families (4.2 %) had mutations in both EXT1 and EXT2. Twenty-four families (33.8 %) did not exhibit mutations in either EXT1 or EXT2. With regard to the types of mutations identified, 59.6 % of mutations were inactivating mutations, and 38.5 % of mutations were missense mutations. We found that the prevalence of EXT1 mutations was greater than that of EXT2 mutations in Japanese MO families. Additionally, we identified 22 novel EXT1 and EXT2 mutations in this Japanese MO cohort. This study represents the variety of genotype in MO. The online version of this article (doi:10.1186/s12863-016-0359-4) contains supplementary material, which is available to authorized users.