Genetic screening of <i>TGFBI</i> in Iranian patients with <i>TGFBI</i>-associated corneal dystrophies and a meta-analysis of global variation frequencies

Transforming growth factor beta-induced (<i>TGFBI</i>)-associated corneal dystrophies (CDs) are a clinically heterogeneous group of CDs caused by mutations in the <i>TGFBI</i> gene. Nucleotide sequences encoding two arginine residues at positions 124 and 555 in TGFBI protein are mutation hotspots. We screened regions of <i>TGFBI</i> that include the hotspots in a cohort of Iranian patients with <i>TGFBI</i>-associated CDs. We also performed a meta-analysis for frequencies of all reported <i>TGFBI</i> mutations. Twenty-four <i>TGFBI</i>-associated CD-diagnosed patients were recruited. Exons 4 and 12 of <i>TGFBI</i> were amplified by the polymerase chain reaction and sequenced by Sanger protocol. A meta-analysis on reported <i>TGFBI</i> sequence data was done by reviewing all published relevant articles available in NCBI. Twenty-two out of 24 patients had mutations in exons 4 or 12 of <i>TGFBI</i>. The most frequent mutations were p.Arg124Cys, p.Arg124His, and p.Arg555Trp; each of these was found in six families. Three other missense mutations including p.Arg555Gln, p.Ile522Asn, and p.Ala546Thr were also identified. The data suggested a fairly tight genotype/phenotype correlation for the most common CDs. Literature review evidenced that the reported mutations affected less than 30% of the amino acids of the TGFBI protein and that p.Arg124His, p.Arg124Cys, p.Arg555Trp, p.Arg124Leu, p.Arg555Gln, and p.His626Arg were the most frequent mutations. <i>TGFBI</i> mutation profile of Iranian patients is very similar to that of the rest of the world. The meta-analysis confirmed the worldwide prevalence of p.Arg124 and p.Arg555, showed that p.His626Arg is also relatively frequent, and evidenced the value of screening exons 4 and 12 of <i>TGFBI</i>.