Molecular genetic study of Egyptian patients with macular corneal dystrophy

Abstract

Aim: To identify the underlying genetic defect in Egyptian patients with macular corneal dystrophy (MCD). Methods:A clinical and molecular genetic study was performed on eleven patients from six families with MCD. Clinical diagnosis was confirmed by slit lamp biomicroscopy and histopathological examination of corneal buttons following keratoplasty. The coding region of the carbohydrate sulfotransferase (CHST6) gene was amplified by polymerase chain reaction (PCR) in all affected subjects. This was followed by direct sequencing and restriction digest analyses. Enzyme-linked immunosorbent assay (ELISA) of antigenic keratan sulfate (KS) in patients' serum was also performed.Results: Six homozygous mutations of which three are novel were identified within the coding region of CHST6 in six unrelated MCD families. The barely detectable level of antigenic KS in the serum of the affected individuals indicated that they all have MCD type I, including the subtype IA.Conclusions: This is the first report of molecular genetic analysis of MCD in the Egyptian population. Our data indicates the extensive allelic heterogeneity within CHST6 and further support its essential role in maintaining corneal transparency.3

Phenotype and genotype analysis in patients with macular corneal dystrophy

“…The R162G polymorphism was identified in German, American and Czech patients 8 9 16. The L200R mutation is a common finding among patients with MCD and was previously reported in American,8 15 British,12 Czech,16 Italian17 and French18 patients. When our results are compared with the two nearest populations, Czech and German, a common finding (the missense mutation L200R with the additional polymorphism R162G) was observed.…”

A Carbohydrate Sulfotransferase‐6 (CHST6) gene mutation is associated with Macular Corneal Dystrophy in Labrador Retrievers

“…The mutation reported in this study (c.814C>A) affects codon 272, which is in a region highly conserved across different CHST proteins and within C‐GlcNAc6ST across different species . More specifically, codon 272 of C‐GlcNAc6ST is conserved in all seven species examined.…”

“…Mutations in the CHST6 gene are responsible for most cases of MCD in humans . Marked allelic heterogeneity has been documented in different populations throughout the world; more than 125 CHST6 mutations have been identified in humans with MCD . The most frequent abnormalities are missense or nonsense single nucleotide polymorphisms (SNPs) that alter a conserved part of the protein.…”

Genetic Analysis of CHST6 Gene in Indian Families with Macular Corneal Dystrophy

“…Of these, we have identified a novel missense mutation in patient from the family 9 that leads to the replacement of glutamic acid to glutamine (E274Q) while in an independent studies from different ethnic background (Egypt, Japanese, American) with MCD; they have identified the same missense mutation (E274K) though the glutamic acid was replaced by lysine and the same mutation was identified in a patient from family 28, but in a heterozygous state suggesting that the second mutation may be present in the deep intronic or regulatory region of CHST6 gene which was not covered by Sanger sequencing [15,18]. This mutation was highly conserved across different orthologous species ( Figure 2).…”

“…The recurrence rate of corneal opacities is more than 40% in macular corneal grafts even after 10 years of Penetrating Keratoplasty (PKP) [7]. CHST6 gene is the only candidate gene so far known in MCD and has been further screened in different ethnic populations across the world [2,3,[8][9][10][11][12][13][14][15][16][17]. It is located on chromosome 16q22 [18,19].…”