Autosomal Recessive CHED Associated With Compound Heterozygous Mutations in SLC4A11

Abstract

Purpose:: To determine the genetic basis of autosomal recessive congenital hereditary endothelial dystrophy (CHED2) in an American patient of Chinese ancestry.

Methods:: Slit lamp examination of the proband and his parents, as well as histopathologic examination of excised corneal specimens from the proband, were performed to confirm the diagnosis of autosomal recessive CHED. DNA was collected from the proband and his parents, and all 19 exons of the SLC4A11 gene were amplified and screened.

Results:: The proband demonstrated diffuse bilateral corneal edema, not present in either of his parents. Following the performance of bilateral penetrating keratoplasties, histopathologic examination of the excised corneal specimens demonstrated marked corneal stromal edema, and an absence of corneal endothelial cells. Screening of SLC4A11 demonstrated two heterozygous mutations, c.743G>A (Ser232Asn) and c.1033A>T (Arg329X). The proband’s mother was found to be heterozygous for the Ser232Asn missense mutation, and his father was heterozygous for the Arg329X nonsense mutation. No other coding region sequence variants were identified in the proband or his parents, and neither of the identified mutations was identified in 100 control individuals.

Conclusions:: CHED2 is associated with mutations in SLC4A11, a member of the SLC4 family of bicarbonate transporters. While all affected individuals reported to date have demonstrated homozygous mutations, associated with consanguinity in the Burmese, Indian and Pakistani populations, we report two novel, independently sorting SLC4A11 mutations in an affected individual of Chinese ancestry.

Keywords: cornea: basic science • gene screening