TGFBI gene mutation in a Chinese pedigree with Reis-Bu ¨ cklers corneal dystrophy Qingfeng Liang, Xuguang Sun and Xiuying Jin Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China Citation information: Liang Q, Sun X & Jin X. TGFBI gene mutation in a Chinese pedigree with Reis-Bu ¨ cklers corneal dystrophy. Ophthalmic Physiol Opt 2012, 32, 74–80. doi: 10.1111/j.1475-1313.2011.00867.x Keywords: mutation, p.Arg124Leu, Reis- Bu ¨ cklers corneal dystrophy, transforming growth factor-b induced (BIGH3) gene Correspondence: Xuguang Sun E-mail address: sunxuguang@yahoo.com.cn Received: 14 April 2011; Accepted: 29 July 2011 Abstract Purpose: To characterize the molecular defects in the TGFBI gene in a Chinese family with Reis-Bu ¨cklers corneal dystrophy (RBCD), and to study the relation- ship between the gene mutations and the clinical manifestations. Methods: Four generations of this family with RBCD were enrolled in the study. In addition to ophthalmic and histopathological examinations, polymer- ase chain reaction (PCR) amplification and analysis of nucleotide sequencing of exons 4, 12, 14 of TGFBI were performed. Results: The clinical manifestations of the disease were characterized by geo- graphic opacities in the subepithelial layers and anterior stroma of the cornea. Confocal microscopy images of the cornea showed focal hyper-reflective mate- rials deposited in the subepithelium and anterior stroma. It was confirmed by histopathology that Bowman’s membrane was mainly replaced by extracellular fibril material, which extended downwards into the superficial corneal stroma. Molecular genetic analysis revealed a single heterozygous G>T change at nucle- otide 124 in exon 4 of TGFBI in all members (22) of the pedigree affected with RBCD, but not in the unaffected members. Conclusions: A p.Arg124Leu mutation of the TGFBI gene was detected in this Chinese pedigree with Reis-Bu ¨cklers corneal dystrophy. The phenotype of Reis- Bu ¨cklers corneal dystrophy in this family belongs to the geographic type. The molecular genetic studies combined with histopathology may be useful for the accurate diagnosis of this type of corneal dystrophy. Introduction Corneal dystrophies (CDs) are defined as a group of corneal disorders that are primary, bilateral, inherited alterations of the cornea, not associated with prior inflammation or systemic diseases (American Academy of Ophthalmology 2007–2008). Recent advances in molecu- lar genetics have revealed the genes responsible for many types of the corneal dystrophies. Mutations of the human transforming growth factor-b induced (TGFBI) gene have been linked to five types of CDs: (1) Granular CD, (2) Lattice CD, (3) Reis–Bu ¨cklers CD, (4) Thiel-Behnke CD, and (5) Granular CD type II, or Avellino type CD. 1 The association of gene mutations with specific phenotypes has given the clinician the opportunity to diagnose corneal dystrophic disorders with molecular genetic analysis. Reis-Bu ¨cklers corneal dystrophy (RBCD/CDB1; OMIM 608470) is an autosomal dominant inherited disease char- acterized by bilateral, superficial corneal opacities caused by mutations in the TGFBI gene on chromosome 5 at q31. To date, five different mutations (p.Arg124Leu, p.Arg124Cys, p.Gly623Asp, p.Arg555Gln, p.Arg555Trp) have been reported to be associated with most cases of RBCD. 1–5 The protein product of the TGFBI gene, kera- toepithelin, is an extracellular matrix protein expressed in the corneal epithelium, which presumably contributes to the structure of the extracellular matrix of the cornea. RBCD primarily affects Bowman’s layer and is character- ized by frequent recurrent attacks of painful cornea Ophthalmic & Physiological Optics ISSN 0275-5408 74 Ophthalmic & Physiological Optics 32 (2012) 74–80 ª 2011 The College of Optometrists