Delayed onset of congenital hereditary endothelial dystrophy due to compound heterozygous SLC4A11 mutations.
BACKGROUND
Congenital hereditary endothelial dystrophy (CHED) is an autosomal recessive disorder characterized by bilateral, symmetrical, noninflammatory corneal clouding (edema) present at birth or shortly thereafter. This study reports on an unusual delayed presentation of CHED with compound heterozygous SLC4A11 mutations.


METHODS
A 45-year-old female, presenting with bilateral decreased vision since childhood that deteriorated in the last 5 years, was evaluated to rule out trauma, viral illness, chemical injury, glaucoma, and corneal endothelial dystrophies. Tear sample was sent for herpes simplex viral (HSV) antigen testing. Genomic DNA from peripheral blood was screened for mutations in all exons of SLC4A11 by direct sequencing. Full-thickness penetrating keratoplasty was done and corneal button was sent for histopathological examination.


RESULTS
Slit-lamp findings revealed bilateral diffuse corneal edema and left eye spheroidal degeneration with scarring. Increased corneal thickness (762 μm and 854 μm in the right and left eyes, respectively), normal intraocular pressure (12 mmHg and 16 mmHg in the right and left eyes, respectively), inconclusive confocal scan, and specular microscopy, near normal tear film parameters, were the other clinical features. HSV-polymerase chain reaction was negative. Histopathological examination revealed markedly thickened Descemet's membrane with subepithelial spheroidal degeneration. SLC4A11 screening showed a novel variant p.Ser415Asn, reported mutation p.Cys386Arg and two polymorphisms, all in the heterozygous state and not identified in 100 controls.


CONCLUSIONS
The study shows, for the first time, compound heterozygous SLC4A11 mutations impair protein function leading to delayed onset of the disease.
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
Babu Lal
BL
Kumawat
Department of Anatomy, Laboratory of Cyto-Molecular Genetics, All India Institute of Medical Sciences, New Delhi, India.
Ranjan
R
Gupta
Department of Anatomy, Laboratory of Cyto-Molecular Genetics, All India Institute of Medical Sciences, New Delhi, India.
Arundhati
A
Sharma
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
Seema
S
Sen
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
Shikha
S
Gupta
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
Radhika
R
Tandon
D017668:Age of Onset; D027321:Anion Transport Proteins / Q000235:genetics* / Q000378:metabolism; D017920:Antiporters / Q000235:genetics* / Q000378:metabolism; D003315:Cornea / Q000000981:diagnostic imaging*; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D063171:Corneal Pachymetry; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D013997:Time Factors
D027321:Anion Transport Proteins; D017920:Antiporters; C425809:SLC4A11 protein, human; D004247:DNA