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B. Sonmez, V. Yellore, S. Rayner, A. Salem, N. Bourla, G. Schultz, A. Aldave; Keratocan (Kera) and Lumican (Lum) Gene Screening in a Family With Autosomal Dominant Cornea Plana (CNA1) . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5554.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the role of KERA and LUM genes in CNA1 by screening members of a multigenerational family affected with autosomal dominant cornea plana.
Slit lamp examination was performed to determine each patient’s affected status. DNA was collected from each individual, following which PCR amplificaiton and sequencing of KERA and LUM genes was performed.
Five affected and and three unaffected individuals were examined and provided a peripheral blood sample for DNA isolation. All affected individuals demonstrated an average corneal dioptric power less than 39 D, as well as one or more of the following anomalies: high hyperopia, strabismus, microcornea, posterior embryotoxon, iridocorneal adhesions, iris atrophy and pupillary irregularities. Screening of the lumican gene revealed that all five affected individuals and one unaffected individual were homozygous for 236InsCC in the 5’UTR; the other two unaffected individuals demonstrated the compound heterozygous 236InsCC/236InsCCA variant. Screening of the KERA gene in affected individuals revealed six known single nucleotide polymorphisms (SNPs) (191A>C, 688G>A, 694G>A, 2313C>T, 2356G>T, 2470C>T) and three novel sequence variants (190T>C, 2076T>G, 2404C>T). However, 688G>A (Val23Val) and 694G>A (Gln25Gln) were the only two SNPs identified in the coding region as the others were identified in the 5’ and 3’ untranslated regions. Each of the six previously identified SNPs was also identified in unaffected family members. The novel 190 T>C variant was present in four affected individuals, but did not sort with the diease phenotype in all individuals as it was not present in the other affected individual and was identified in an unaffected family member. Similarly, the novel 2076T>G and 2404C>T variants were present in two affected individuals, but were also identified in an unaffected individual and were not present in the other three affected individuals. None of the mutations previously associated with CNA2 (Asn131Asp, Gln174X, Lys215Thr, Asn247Ser, Arg279X and Arg313X) were identified.
Although missense and nonsense mutations in the KERA gene are associated with autosomal recessive cornea plana (CNA2), we did not identify any of the previously described mutations or novel mutations that sorted with the disease phenotype in a family with CNA1. Additionally, no pathogenic sequence variations were present in the LUM gene, which has also been implicated in the pathogenesis of cornea plana.
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