A Candidate Gene for Cerebro-Oculo-Nasal Syndrome: A Zinc-Finger Gene ZNF185 Located at Xq28

Cerebro-oculo-nasal syndrome (CONS) is characterized by ocular alterations ranging from anophthalmia/microphthalmia to normal eyes, structural anomalies of the central nervous system, and proboscis-like nares. This syndrome was first described more than 30 years ago, but only 21 patients have been reported to date.

In the present report, we present a 20-year-old CONS patient who exhibited anophthalmia, microphthalmia, cleft lip-palate, and proboscis-like nares. Exome sequencing (ES) analysis was performed for clinical diagnosis for the index case; her parents were evaluated with Sanger sequence analysis methods in terms of the variation detected in the index case. The ES analysis of the patient identified a novel heterozygous frameshift variant in the ZNF185 gene. This variant was not detected in her parents, whose biological relationship to the patient was confirmed through identity testing. According to the American College of Medical Genetics and Genomics (ACMG) criteria, this novel de novo variant was assessed as likely pathogenic. Peripheral blood mononuclear cells were isolated from peripheral blood of the patient and her parents. Protein was extracted and analyzed by Western blot using antibodies against ZNF185 and GAPDH as control. Western blot analysis detected an ∼80 kDa protein in both the patient and her healthy parents. Additionally, extra bands (∼20-25 kDa) were observed in the patient using the anti-ZNF185 antibody.

We aimed to evaluate all CONS patients based on their clinical features. Furthermore, we propose that the ZNF185 gene may play a role in the etiology of CONS.