Intractable Rare Dis Res. 2020;9(1):48-53. (DOI: 10.5582/irdr.2019.01109)

Characterization of a novel pathogenic variation c.1237T>G in the FZD4 gene presenting new inheritance from an Iranian individual suffering vitreoretinopathy

Zamani M, Shariati G, Seifi T, Sedaghat A, Galehdari H


Whole Exome Sequencing (WES) has been used increasingly in genetic determination of various known and unknown genetic disorders. Various genes are involved in the development of the vascular network of retina. Assessment of a collection of these genes could be provided by WES. Here we used WES for a patient suffering vitreoretinopathy to detect the disease causing variant. Sanger sequencing has been applied for variant verification and allelic segregation. After analysis of WES data we found a new variant c.1237T>G in the FZD4 locus which causes retinopathy of prematurity and exudative vitreoretinopathy (MIM number: 133780). Sanger sequencing showed this single nucleotide variation inherited as homozygous in the patient and heterozygous in her unaffected parents. Notably, bioinformatics analysis predicted the variant as disease causing and it has not been described yet in home datasets and public SNP databases. FZD4 mutations are mostly inherited as autosomal dominant traits. Our findings showed the first autosomal recessive inheritance of the FZD4 gene related retinopathy. On the other hand, our data shed light on the significance of an Exome sequencing application as a genetic test to identify and characterize the comprehensive spectrum of genetic variation and classification for patients with retinopathies.

KEYWORDS: exome sequencing, FZD4, vitreoretinopathy, autosomal recessive

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