Mutation analysis of the SLC4A11 gene in Indian families with congenital hereditary endothelial dystrophy 2 and a review of the literature

Abstract

Purpose: Congenital hereditary endothelial dystrophy 2 (CHED2) is an autosomal recessive disorder caused by mutations in the solute carrier family 4, sodium borate transporter, member 11 (SLC4A11) gene. The purpose of this study was to identify the genetic cause of CHED2 in six Indian families and catalog all known mutations in the SLC4A11 gene.

Methods: Peripheral blood samples were collected from individuals of the families with CHED2 and used in genomic DNA isolation. PCR primers were used to amplify the entire coding region including intron-exon junctions of SLC4A11. Amplicons were subsequently sequenced to identify the mutations.

Results: DNA sequence analysis of the six families identified four novel (viz., p.Thr262Ile, p.Gly417Arg, p.Cys611Arg, and p.His724Asp) mutations and one known p.Arg869His homozygous mutation in the SLC4A11 gene. The mutation p.Gly417Arg was identified in two families.

Conclusions: This study increases the mutation spectrum of the SLC4A11 gene. A review of the literature showed that the total number of mutations in the SLC4A11 gene described to date is 78. Most of the mutations are missense, followed by insertions-deletions. The present study will be helpful in genetic diagnosis of the families reported here.

Figure 1

Deoxyribonucleic acid sequence analysis of individuals. Sequencing chromatograms of the heterozygous parents and affected homozygous individuals from family 3, 4, 5, 6, 7, and 8 are shown. Arrows mark the nucleotide change in a heterozygous state in parents and in a homozygous state in affected individuals. + and m denote the wild type and the mutant alleles.

Figure 2

Clinical features of affected individual II-1 from family 7. A: Cornea showing opacification. B: Slit-lamp examination of the cornea showing thickening and opacification.

Figure 3

Conservation of the amino acid residues across different species. Arrows mark the conservation of mutated amino acid residues Cys611, Gly417, His724, and Thr262 across different species in SLC4A11. The number refers to the position of the amino acid residue.