Rozzo C, Fossarello M, Galleri G, Sole G, Serru A, Orzalesi N, Serra A, Pirastu M
Istituto di Genetica Molecolare, C.N.R., Alghero, Italy.
Hum Mutat. 1998;12(3):215-6.
Reis-Bücklers' corneal dystrophy (RBCD) is a relatively rare autosomal dominant disease originating in the Bowman's membrane, which causes severe visual impairment. Recently RBCD, together with lattice corneal dystrophy type I (LCDI), granular corneal dystrophy (CDGG1) and Avellino stromal dystrophy (ASD), all mapped on 5q31, were found to be associated to four different mutations in the beta ig-h3 gene which codify for kerato-epithelin. We identified several cases of RBCD in Sardinia. We reconstructed through genealogical search two eight generation-families, originating from the same village (Arbus), indicating a common ancestor for RBCD in Sardinia. Linkage studies on these families confirmed the association of the disease with the 5q31 region. Sequence analysis of beta ig-h3 gene revealed a trinucleotide deletion in exon 12, corresponding to the loss of F540 in the protein sequence (delta F540). Our data describe a new mutation in the beta ig-h3 gene causing RBCD. This dominant negative mutation is located in the fourth internal repeat of kerato-epithelin which is a protein domain highly conserved across species. This suggests the basic role of this domain in maintaining the proper kerato-epithelin structure which when altered can cause the typical precipitates in the RBCD cornea.
赖斯 - 比克勒角膜营养不良（RBCD）是一种相对罕见的常染色体显性疾病，起源于鲍曼层，可导致严重视力损害。最近发现，RBCD与I型格子状角膜营养不良（LCDI）、颗粒状角膜营养不良（CDGG1）和阿韦利诺角膜基质营养不良（ASD）一样，都定位于5q31，它们与βig-h3基因中的四种不同突变相关，该基因编码角膜上皮素。我们在撒丁岛发现了几例RBCD病例。通过家谱搜索，我们重建了两个起源于同一个村庄（阿尔布斯）的八代家族，表明撒丁岛的RBCD有一个共同的祖先。对这些家族的连锁研究证实了该疾病与5q31区域的关联。βig-h3基因的序列分析显示外显子12中有一个三核苷酸缺失，对应于蛋白质序列中F540的缺失（ΔF540）。我们的数据描述了一种导致RBCD的βig-h3基因新突变。这种显性负性突变位于角膜上皮素的第四个内部重复序列中，这是一个在物种间高度保守的蛋白质结构域。这表明该结构域在维持角膜上皮素的正确结构中起基本作用，当结构改变时可导致RBCD角膜中出现典型的沉淀物。
