Biallelic novel variants in ZNF469 causing Brittle Cornea Syndrome 1: a detailed report of an Indian patient.

Abstract

Background: Variations in ZNF469 have been associated with Brittle Cornea Syndrome that presents with bluish sclera, loss of vision after trivial trauma, arachnodactyly, and joint laxity.

Materials and methods: Detailed medical and family history, physical examination, and molecular analysis.

Results: A 21-year-old female presented with bluish discoloration of sclera, diminution of vision following trivial trauma in childhood along with hearing loss and systemic features of arachnodactyly and joint laxity. Clinical diagnosis of brittle cornea syndrome was made which was molecularly proven using next-generation sequencing which identified compound heterozygosity in ZNF469 for pathogenic and likely pathogenic nonsense variants. One variant namely NM_001367624.2:c.5882dup was identified in the exon 3 which was novel and classified as likely pathogenic according to American College of Medical Genetics (ACMG) criteria for variant classification. Another variant NM_001367624.2:c.8992C>T in the exon 2 was classified as pathogenic for Brittle Cornea Syndrome 1.

Conclusions: The report adds to the allelic heterogeneity in ZNF469 causative of Brittle Cornea Syndrome 1 and shall acquaint the physicians about this potentially vision threatening, underdiagnosed, rare syndrome.