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Inderjeet Kaur, sonika rathi, Ganeswara Musada, Subhadra Jalali, Ramesh Kekunnaya, Pramod Gaddam, Subhabrata Chakrabarti; Genetic Screening of TSPAN12, NDP and FZD4 Genes in Indian Patients with Retinopathy of Prematurity. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6204.
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Retinopathy of prematurity (ROP) is a vaso-proliferative eye disease in prematurely born infants. The clinical manifestation of this condition exhibits similarites with Familial Exudative Vitreo-retinopathy (FEVR). Genes involved in the Wnt signalling pathway (TSPAN12, NDP, FZD4) have been implicated in retinal neovascularisation among FEVR patients. Thus, a similar molecular mechanism could be envisaged underlying ROP based on its phenotypic similarities with FEVR. In the present study, we aimed to assess the role of TSPAN12, NDP, FZD4 genes in ROP.
The TSPAN12, NDP and FZD4 genes were screened in ROP patients (n=200) and controls consisting of mature (n=127) and premature babies devoid of ROP (n=147). Screening was accomplished by resequencing using specific sets of primers to amplify the entire coding and untranslated regions (UTR) in these genes using the BigDye chemistry. The observed variants were further validated by restriction digestion and characterized for mutations or polymorphisms.
The TSPAN12 gene screening led to the identification of a heterozygous mutation in a patient with threshold ROP (L119V), a novel SNP (c.*334A>T) and three reported SNPs (rs41623, rs41622, rs189221112) in the study cohort. There were no significant differences in the allele or genotype frequencies of these SNPs between the ROP patients and controls. Two novel variations viz., IVS1+16A>G in the intron 1 and c.1503T>C in 3’UTR region and a previosuly reported change in the 5’UTR region (c.171_184del14bp) were observed in the NDP gene in 3 ROP patients. Extended screening of the FZD4 also revealed two heterozygous variations I192I and I360V and three reported SNPs (rs61735303, rs201168680, rs61749246) in the study cohort. However, a formal genotype-phenotype corelation could not be established due to the low frequencies of the variant alleles in these genes.
These results suggest a minor involvement of TSPAN12, NDP and FZD4 genes with ROP. Unlike FEVR, ROP may be genetically more heterogeneous with multiple alleles with varying magnitudes of effect.
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