Autosomal recessive CHED associated with novel compound heterozygous mutations in SLC4A11.
OBJECTIVE
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 showed diffuse bilateral corneal edema, which was not present in either of his parents. After the performance of bilateral penetrating keratoplasties, histopathologic examination of the excised corneal specimens showed marked corneal stromal edema and an absence of corneal endothelial cells. Screening of SLC4A11 showed 2 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 base transporters. Although the majority of affected individuals reported to date have shown homozygous mutations, associated with consanguinity in the Burmese, Indian, and Pakistani populations, we report 2 novel, independently sorting SLC4A11 mutations in an affected individual of Chinese ancestry.
Cornea Service, The Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. aldave@jsei.ucla.edu
Anthony J
AJ
Aldave
Vivek S
VS
Yellore
Nirit
N
Bourla
Rominder S
RS
Momi
M Ali
MA
Khan
Andrew K
AK
Salem
Sylvia A
SA
Rayner
Ben J
BJ
Glasgow
Ira
I
Kurtz
D000293:Adolescent; D027321:Anion Transport Proteins / Q000235:genetics*; D017920:Antiporters / Q000235:genetics*; D001213:Asian / Q000235:genetics; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000601:surgery; D015715:Corneal Edema / Q000235:genetics / Q000601:surgery; D005091:Exons / Q000235:genetics; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D015948:Keratoplasty, Penetrating; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction
D027321:Anion Transport Proteins; D017920:Antiporters; C425809:SLC4A11 protein, human