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Pablo Romero, Rodrigo Donoso, Dominique Chrzanowsky, Pamela Lopez, Luisa Herrera; Small duplication mutation in the SLC4A11 gene causing Corneal Dystrophy and Perceptive Deafness (CDPD) in three Chilean families . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2520.
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© ARVO (1962-2015); The Authors (2016-present)
To report the clinical, ophthalmic, and genetic characteristics of a rare disorder, Corneal Dystrophy and Perceptive Deafness (CDPD) or Harboyan syndrome, in five members of three Chilean families.
Five individuals affected with CDPD and five unaffected persons from three apparently unrelated families were clinically examined, including visual acuity, slit lamp biomicroscopy and fundoscopy. A thorough ear, nose and throat (ENT) examination was carried out. Genomic DNA was extracted from peripheral leukocytes from the five affected and five unaffected subjects. Screening for mutations in exons 16-18 of the SLC4A11 gene was performed by DNA sequencing. 7 SNPs were analyzed in all the subjects and in 87 individuals of the population to evaluate a putative founder effect.
Based on ophthalmic and otolaryngology alterations five subjects were diagnosed with CDPD. All affected presented some degree of sensorineural hearing loss. The ophthalmic symptoms started between birth and age 1 year, while hearing symptoms began after 8 years of age. The ophthalmic alterations were bilateral and symmetric in all the affected. All patients needed penetrating keratoplasty and visual acuity varied from 0.1 to 0.3 post keratoplasty. The sequence of the SLC4A11 gene of the probands of the three families exhibited a homozygous eight nucleotide sequence duplication (c.2233_2240dup TATGACAC) at the end of exon 16. This mutation was not present in 98 healthy controls. The predicted protein sequence encoded by the mutated gene would be a truncated protein of 757 out of the normal 891 amino acids, including the first 9 and lacking the last five transmembrane domains. The haplotypes contructed using 7 SNPs covering 12 MB were not identical in the affected patients of different families although all of them shared a 4,1Mb haplotype.
Five subjects were positively diagnosed with CDPD with ophthalmic and otolaryngologic symptoms. They were homozygous for a sequence duplication of eight nucleotide (c.2233_2240dup TATGACAC) in the SLC4A11 gene, which co-segregated with CDPD in the three studied families. The haplotype analysis was in accordance with a founder effect. This is the first report of a molecular analysis of CDPD in Chilean patients and is the second report of the eight nucleotide sequence duplication in patients with CDPD worldwide.
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