Corneal dystrophies in Japan
Corneal dystrophies in Japan
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DOI：
10.1007/s100380170041
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发表时间：
2001-01-01
影响因子：
3.5
通讯作者：
Kanai, A
中科院分区：
文献类型：
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作者：
Fujiki, K;Nakayasu, K;Kanai, A
分子遗传学的最新进展增加了我们对基因作用的认识。4例常染色体显性角膜营养不良（CDs）；将颗粒型CD （GCD）、Avellino型CD （ACD）、点阵型CD （LCD）和Reis-Bucklers型CD （RBCD）定位于5号染色体长臂（5q31）。在高加索系列中，这四种疾病显示是由TGFBI （BIGH3，角膜上皮蛋白）基因的不同错义突变引起的。在来自不同种族背景的日本患者中也检测到相同的突变。另一方面，1914年在日本患者中发现的胶滴样角膜营养不良（GDLD）是一种罕见的常染色体隐性遗传病，以角膜淀粉样变性为特征。患者父母的近亲结婚频率明显高于一般人群。将负责GDLD、膜组分、1号染色体、表面标记1（M1S1）基因定位到1号染色体短臂（lp）上。在日本患者中检测到该基因的四种有害突变。我们在此回顾了在日本患者中发现的TGFBI和M1S1基因突变的其他研究。TGFBI基因在日本GCD、ACD、LCD和RBCD患者中检测到9种不同的突变。TGFBI基因的密码子R124和R555是日本患者的热点，其中以R124H突变的ACD患者较多。在LCD患者的TGFBI基因中发现了与LCD相关的新突变，而之前在LCD IIIA型中发现了P501T突变。这些研究表明TGFBI基因具有明显的基因型/表型相关性。如前所述，在M1S1基因中，Q118X突变是最常见的变异，也是日本GDLD患者的创始突变。92%的突变等位基因是Q118X。
Recent advances in molecular genetics have increased our understanding of the role of genes. Four autosomal dominant corneal dystrophies (CDs); granular CD (GCD), Avellino CD (ACD), lattice CD (LCD), and Reis-Bucklers CD (RBCD) were mapped to the long arm of chromosome 5 (5q31). These four diseases were shown, in a Caucasian series, to result from different missense mutations in the TGFBI (BIGH3, keratoepithelin) gene. The same mutations were also detected in Japanese patients, from a different ethnic background. Gelatinous drop-like corneal dystrophy (GDLD), on the other hand, which was found in Japanese patients in 1914, is a rare autosomal recessive disorder characterized by corneal amyloidosis. Parents of the patients had a markedly higher frequency of consanguineous marriages than the general population. The gene responsible for GDLD, the membrane component, chromosome 1, surface marker 1 (M1S1) gene was mapped to the short arm of chromosome 1(lp). Four deleterious mutations in this gene were detected in Japanese patients. We review here additional studies on mutations of the TGFBI and M1S1 genes found in Japanese patients. In the TGFBI gene, nine different mutations were detected in Japanese patients with GCD, ACD, LCD, or RBCD. The codons R124 and R555 of the TGFBI gene were hotspots in Japanese patients, of whom many were ACD patients with the R124H mutation. New mutations responsible for LCD were detected in the TGFBI gene of patients with LCD, in addition to the P501T mutation in LCD type IIIA found earlier. These studies showed a clear genotype/phenotype correlation associated with the TGFBI gene. In the M1S1 gene, the Q118X mutation was the most common alteration, and a founder mutation in Japanese GDLD patients, as previously reported. Ninety-two percent of the mutated alleles were the Q118X.