TGFBI gene mutations in the Ukrainian patients with inherited corneal stromal dystrophies

Transforming growth factor beta‐induced p.(L558P) variant is associated with autosomal dominant lattice corneal dystrophy type IV in a large cohort of Spanish patients

“…The pathogenicity of p.(L558P) variant was initially supported by its autosomal dominant co-inheritance with the atypical CD in our cohort of Spanish families. Similar findings have been reported in four Ukrainian families 14,28 and a different Spanish family. 10 Moreover, the absence of reported frequency values in different genomic databases such as ExAC and Ensembl, the high evolutionary conservation of the mutated amino acid and the predicted damaging effect on protein function, further support the deleterious effect of this variant.…”

Variant lattice corneal dystrophy associated with compound heterozygous mutations in theTGFBIgene

“…The phenotype in the family that we report differs considerably from the phenotype previously reported in association with the p.(Val113Ile) mutation, resembling more the clinical phenotype of ‘polymorphic corneal amyloidosis’ that has been used to describe the appearance of individuals with atypical LCD associated with the p.(Leu558Pro) mutation 9. To the best of our knowledge, only six families have been reported with affected individuals who are heterozygous for two different TGFBI mutations (table 1).…”

“…Screening of TGFBI exons 1–17 in the proband demonstrated two previously described heterozygous missense mutations, c.384G>A (p.(Val113Ile)) in exon 4 and c.1673T>C (p.(Leu558Pro)) in exon 12 (figure 1), and a common synonymous substitution, c.651G>C (p.(Leu217Leu)), in exon 6 (MAF=0.318) 8 9. Screening of TGFBI in the proband's 43-year-old affected sister (figure 1; II-3) demonstrated the same missense and silent mutations present in the heterozygous state.…”

“…We describe the clinical and histopathological features of a novel variant LCD associated with the p.(Val113Ile) and p.(Leu558Pro) mutations in the TGFBI gene. As p.(Val113Ile) has been previously described in association with a GCD phenotype, the p.(Leu558Pro) mutation appears to be the major determinant of the resultant phenotype, a novel variant of LCD 8 9…”

IL1β, IL6 and IL8 gene polymorphisms involvement in recurrent corneal erosion in patients with hereditary stromal corneal dystrophies

“…LCD type I and type IIIA have been reported to be caused by specific point mutations in the TGFBI (transforming growth factor beta-induced) gene and to have autosomal dominant inheritance pattern. The main mutations associated with LCD in Ukrainian patients are Hys626Arg (type IIIA) and Arg124Cys (type I) in TGFBI gene with respective frequencies of 0,416 and 0,375 [4]. Accumulation deposits accumulation in patients with hereditary stromal corneal dystrophies (HSCD) leads to impaired attachment of epitheliocytes to basement membrane -corneal erosion.…”