Macular corneal dystrophy: mutational spectrum in German patients, novel mutations and therapeutic options
Macular corneal dystrophy: mutational spectrum in German patients, novel mutations and therapeutic options
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DOI：
10.1007/s00417-008-0836-1
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发表时间：
2008-10-01
影响因子：
2.7
通讯作者：
Duncker, Gernot I. W.
中科院分区：
文献类型：
--
作者：
Gruenauer-Kloevekorn, Claudia;Braeutigam, Saskia;Duncker, Gernot I. W.
介绍本研究的目的是探讨基因型-表型的相关性，手术治疗的后果，和治疗的选择，在黄斑角膜营养不良（MCD）的患者。材料和方法我们调查MCD基因型，采用聚合酶链反应，然后直接测序在一个家庭和四名患者MCD。结果通过限制性内切酶分析证实。结果CHST 6基因编码区发现5个突变，4个错义突变，1个移码突变，其中3个为新突变，1个为单核苷酸多态性突变。在3例患者中，2例在起始密码子（Met 1 Leu）内具有纯合突变，1例具有杂合突变（Leu 200 Arg）和多态性（Arg 162 Gly），具有不规则角膜表面和复发性糜烂，光疗性角膜切除术导致短暂成功。在一名患者中额外验配硬性透气性接触镜可进一步改善不规则散光。在两名患者中，一个移码突变（1734_1735delTG; Arg 211 Gln）和一个两个复合杂合突变（Leu 200 Arg; Leu 173 Phe）和一个额外的多态性（Arg 162 Gly）穿透性角膜移植术改善BCVA没有任何复发的混浊在后续time.Discussion不同的基因型意味着几个表型，这影响治疗程序中MCD患者。我们的研究显示了广泛的诊断结果和治疗选择的患者患有黄斑角膜营养不良取决于基因型。
Introduction The objective of this study was to investigate genotype-phenotype correlations, the consequences for surgical treatment, and the therapeutical options in patients with macular corneal dystrophy (MCD).Material and methods We investigated MCD genotype by using polymerase chain reaction followed by direct sequencing in one family and four patients with MCD. Results were confirmed by restriction analysis. Clinical phenotypes, histopathological findings, and therapeutical proceedings of each patient were reported and compared with the molecular genetic results.Results Five mutations, four missense mutations, and one frameshift mutation, from which three were novel, and one single-nucleotide polymorphism, were identified within the coding region of the CHST6 gene. In three patients, two with a homozygous mutation within the start codon (Met1Leu) and one with a heterozygous mutation (Leu200Arg) and a polymorphism (Arg162Gly), with irregular corneal surface and recurrent erosions a phototherapeutic keratectomy lead to a transient success. An additional fitting of rigid gas permeable contact lenses in one patient could further improve irregular astigmatism. In two patients, one with a frameshift mutation (1734_1735delTG; Arg211Gln) and one with two compound heterozygous mutations (Leu200Arg; Leu173Phe) and an additional polymorphism (Arg162Gly) a penetrating keratoplasty improved BCVA without any recurrence of the opacities within the follow-up time.Discussion Different genotypes imply several phenotypes, which influence therapeutical proceedings in MCD patients. Our study shows the wide range of diagnostic findings and therapeutical options in patients suffering from macular corneal dystrophy depending on the genotype.