Molecular genetic analysis of a Chinese Avellino corneal dystrophy family

Abstract

Background Previous studies demonstrated that the transforming growth factor beta induced (TGFβⅠ) gene is the most common disease-causing gene for corneal dystrophy.However,if DNA variant is associated with phenotype is unclear.Objective This study was to identify the clinical features and molecular genetics of a Chinese family with Avellino corneal dystrophy (ACD) and analyze the association between TGFβⅠ mutation and phenotype.Methods This study complied with Helsinki Declaration and was approved by Ethic Commission of Shenzhen Eye Hospital.Informed consent was obtained from each individual prior to any medical examination.A Chinese ACD family was collected with 19 members of 3 generations.The corneas were clinically examined by slit lamp microscope,ocular anterior segment opitical coherence tomography (OCT) and laser scanning confocal microscope in 5 affected members and 13 unaffected subjects.The peripheral blood sample of 2 ml was collected for the TGFβⅠ mutation analysis (17 exons) and DNA sequencing.Results The proband was diagnosed as ACD.Total 6 patients were found in the pedigree,and 1 male patient dead.This family accorded with an autosomal dominant in heritance pattern.The morphology of corneal opacification showed the bread crumbs-like,stripes-like and patchy-like,and that of male patients was dots-like.The lesion size was larger in female patients than that in male patients.The visual acuity was 0.4-0.9 in female patients and 1.0 in male patients.The findings of OCT and laser scanning confocal microscope were similar between the female and male patients.Sequencing of TGFBI gene revealed a heterozygous transition (c.372 G＞A) in exon 4,which resulted in Arg124His (R124H) being co-segregated with the disease in affected family members,but not in the unaffected members.The single nucleotide polymorphism (SNP) also was seen in exon 8 and 12 (c.981G＞A,V327V and c.1626T＞C,F542F) in affected members.No these variants were detected in the unaffected family members.Conclusions This study confirms that a G ＞ A transition in Arg124His of TGFBI is responsible for the pathogenesis of the Chinese ACD pedigree.The phenotype of female patients appears to be worse than that of the male patients.There is no certain evidence to verify the association between the genotype and phenotype. Key words: Corneal dystrophy, hereditary; Transforming growth factor beta/genetics; Genetic predisposition to disease; DNA mutational analysis; Genotype; Phenotype; Pedigree