Molecular Genetic Analysis In A Chinese Family With Avellino Corneal Dystrophies

Background Corneal dystrophy (corneal malnutrition) is a rare genetic disease whichcan cause serious loss of vision.It can be divided into many types. The type associatedwith TGFBI (transformation growth factor β induced mutation) was studied most,including typical granularity corneal dystrophies (GCD, CDGG I), lattice shape cornealdystrophies (CDL), Avellino corneal dystrophies (GCD-II), and Reis-Bucklers cornealdystrophies (RBCD). Avellino corneal dystrophy is an early onset disease with highpenetrance and show no significant difference in sexuality.Objective This study was to analyze the mutation characteristics and classification ofTGFBI gene in a family with Avellino corneal dystrophies.Methods This family was diagnosed as Avellino corneal dystrophy by The FirstAffiliated Hospital of Anhui Medical University,including4patients and2unaffectedmembers, compared to50healthy controls.All the participants were conducted withroutine eye examination and we extracted DNA from their periphery blood. Then allexons of the TGFBI gene were amplified by the polymerase chain reaction (PCR). Theproducts by PCR were sequenced directly and the new sequences were analyzed byGenBank software.Results Directly sequencing of all affected members revealed a G to A transition inexon4(CGC to CAC,R124H),while unaffected family members and50normal controlsdidn’t show the gene mutation. All the affected members showed a C to T transition inexon11(CTC to CTT, L472L) and3affected members showed a T to C transition inexon12(TTT to TTC, F540F). One affected member had the homozygotic codon (TTT to TTC, F540F).One unaffected family member had the SNP(TTT to TTC), while theother unaffected family member and50normal controls didn’t.Conclusion A R124H heterozygous mutation of the TGFBI gene was found in thefamily with corneal dystrophy. We consider that the R124H heterozygous mutation inexon4is one of the pathogenic factors of corneal dystrophy.