| Purpose：1. To obtain clinical and genetical information of a family affected withReis-Bucklers corneal dystrophy (RBCD)，and to build digital database that storesthese information.2. To describe the clinical phenotype and genetic characteristic of this RBCDfamily.3. To screen all the exons of the candidate TGFBI gene, to search for potentialdisease causing mutations.Methods：1. Collecting and preserving clinical resources of this RBCD family (namingHN-SY-001) including signing informed consents, filling out RBCD questionnaire,drawing the pedigree chart. All subjects filed systematic and comprehensive medicalhistories, and implemented ophthalmologic examinations that embraces best correctedvisual acuity, intraocular pressure (IOP), slit lamp examination, cornea photographing,shirmer test and cornea sensitivity test.2.8~10ml of the peripheral blood were extracted from all the members of thisfamily. Polymeasreehaineraction (PCR) and direct sequencing were implemented toscreen all the16exon regions of the TGFBI gene. Once alterations of the sequenceswere detected, they were compared with the one thousand genome project and theensemble data base. subsequently, candidate mutations were verified in patients and100normal unaffected individuals through direct sequencing.Results:1. The electronic records of clinical database and blood samples database ofRBCD family was scientifically and normatively established in accordance with theinternational and domestic genetic resources collection principle. 2. Nine affected members were diagnosed as Reis-Bucklers corneal dystrophy,with the disease onset age between1~10（3.67±0.90）years. the Initial symptomsinclude photophobia, eyes sworing. The age of visual decline are6~13（8.00±0.78）years. Indivisuals manifest mainly map like epithelial colobama, opacities spreadingover the superficial regions of the stroma, brown pigmentations deposit in the deeperpart of the stroma, and the edema of the stroma. Cornea sensitivity decline were seenin all patients of the cohort.3. A heterozygous missense mutation c.418G>T（p. R124L） in exon4of TGFBIhas been detected in members affected with Reis-Bucklers cornea dystrophy. Thismuation was found to segerate with the phenotype of this cohort, and was foundabsent in100normal control people.Conclusions：1. In this cohort, RBCD patients caused by the TGFBI c.418G>T mutationpoccessed marked phenotype heterogeneity. Unlike the cases previously reported,cornea edema affects the whole layer of the stroma.2. The RBCD family was an autosomal dominant corneal dystrophy family. Thisdisease causing mutation, c.733T＞G transition in exon4of TGFBI was thepathogenetic gene mutation of RBCD family. This discovery enriched the clinicalspectrum of TGFBI. |
