A novel mutation of M1S1 gene found in a Vietnamese patient with gelatinous droplike corneal dystrophy.
A novel mutation of M1S1 gene found in a Vietnamese patient with gelatinous droplike corneal dystrophy.
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在一名患有凝胶状水滴状角膜营养不良的越南患者中发现了 M1S1 基因的新突变。
DOI：
10.1016/s0002-9394(02)01952-9
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发表时间：
2003
影响因子：
4.2
通讯作者：
A. Kanai
中科院分区：
文献类型：
--
作者：
N. T. Ha;H. M. Chau;L. Cung;T. K. Thanh;K. Fujiki;A. Murakami;A. Kanai
目的鉴定越南一个家庭凝胶滴样角膜营养不良（GDLD）的M1S1基因的遗传缺陷。DESIGNExperimental研究。方法采集1例患者和未受gdld影响的家庭成员的血液样本。50名无血缘关系的越南裔正常受试者作为对照。从血液白细胞中提取基因组DNA。采用聚合酶链反应和直接测序对M1S1基因进行DNA分析。结果M1S1基因测序结果显示，在772 ~ 783核苷酸位置[772 ~ 783del(ATCTATTACCTG)]缺失了一个12个碱基对（bp）片段，导致密码子258 ~ 261 （L258-liter261del）缺失4个氨基酸。然而，在缺失的序列（772insT）上发现了核苷酸T的插入。这种组合突变在受gdld影响的患者中是纯合的，而在他未受影响的儿子和妹妹中是杂合的。这种基因改变在对照人群中被排除。结论：这是对越南GDLD患者进行的首次突变分析报告。在这个家族中，M1S1基因上的772 ~ 783del(ATCTATTACCTG) + 777inst突变与表型共分离良好，因此预计会导致GDLD。虽然M1S1基因导致越南患者的GDLD，但这里发现的突变与之前报道的日本患者的突变完全不同，日本患者的GDLD最常见。
PURPOSETo identify the genetic defect in the M1S1 gene responsible for gelatinous droplike corneal dystrophy (GDLD) in a Vietnamese family.DESIGNExperimental study.METHODSBlood samples were collected from a patient and the unaffected members of a GDLD-affected family. Fifty normal unrelated subjects of Vietnamese origin were used as controls. Genomic DNA was extracted from blood leukocytes. DNA analysis of the M1S1 gene was performed using polymerase chain reaction and direct sequencing.RESULTSSequencing of the M1S1 gene revealed a deletion of a 12–base-pair (bp) fragment from nucleotide positions 772 to 783 [772 to 783del(ATCTATTACCTG)], resulting in a loss of four amino acids at codons 258 to 261 (L258-liter261del). Yet, an insertion of nucleotide T in place of the missing sequence (772insT) was found. This combined mutation was homozygous in the GDLD-affected patient and heterozygous in his unaffected son and younger sister. Such genetic alteration was excluded in the control population.CONCLUSIONThis is the first report of a mutational analysis performed in a Vietnamese patient with GDLD. In this family, the novel 772 to 783del(ATCTATTACCTG) + 772insT mutation on the M1S1 gene was well cosegregated with the phenotype and thus expected to cause GDLD. Although the M1S1 gene was responsible for GDLD in Vietnamese patients, the mutation found here is completely different from that previously reported in Japanese patients, where GDLD is most frequently seen.