Two mutations in the transforming growth factor beta-induced gene associated with familial Lattice corneal dystrophy

AIM：To report a phenotypic variant pedigree of lattice corneal dystrophy（LCD）associated with two mutations,R124C and A546 D,in the transforming growth factor betainduced gene（TGFBI）.METHODS：A detailed ocular examination was taken for all participants of a LCD family. Peripheral blood leukocytes from each participant were extracted to obtain the DNA. Polymerase chain reaction（PCR）of all seventeen exons of TGFBI gene was performed. The products were sequenced and analyzed. Histological examination was carried out after a penetrating keratoplasty from the right eye of proband. RESULTS：Genetic analysis showed that the proband and all 6 affected individuals harbored both a heterozygous CGC to TGC mutation at codon 124 and a heterozygous GCC to GAC mutation at codon 546 of TGFBI. None of the 100 control subjects and unaffected family members was positive for these two mutations. Ocular examination displayed multiple refractile lattice-like opacities in anterior stroma of the central cornea and small granular deposits in the peripheral cornea. The deposits were stained positively with Congo red indicating be amyloid in nature and situated mainly in the anterior and middle stroma. CONCLUSION：We observed a novel LCD family which carried two pathogenic mutations（R124C and A546D）in the TGFBI gene. The phenotypic features were apparently different from those associated with corresponding single mutations. The result reveals that although the definite mutation is the most important genetic cause of the disease,some different modifier alleles may influence the phenotype.

Clinicopathological characteristics of human epidermal growth factor receptor 2-positive Barrett's adenocarcinoma

AIM:To compare the clinicopathological characteristics of human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative Barrett's adenocarcinoma in Japan. METHODS:We performed immunohistochemical analysis of HER2 in 30 samples taken from patients with Barrett's adenocarcinoma and dual color in situ hybridization in cases showing 2+ reactions. We compared the clinicopathological characteristics of HER2-positive and HER2-negative patients.RESULTS:HER2 positivity was identified in 8 (27%) carcinoma samples. We found that HER2 expression was associated with p53 overexpression (100% vs 52.6% in pT1 tumor; 100% vs 54.5% in all stage tumor, P < 0.05) and protruding lesions at the early disease stage. There was no association between the mucin phenotype of the carcinomas and prognosis. HER2 expression and low clinical stage were unexpectedly different between Barrett's adenocarcinoma patients and gastric cancer patients, but the macroscopic features may be associated with earlier diagnosis in these patients. CONCLUSION:Our results suggest that HER2-positive Barrett's adenocarcinomas are associated with p53 overexpression and lesion protrusion at the early disease stage.