Novel Pathogenic Variant Confirms the Association of REST and Jones Syndrome.

Abstract

Jones syndrome (JS) is an ultra-rare autosomal dominant condition characterized by gingival fibromatosis and progressive sensorineural hearing loss. It has been recently demonstrated in members of a Finnish family to co-segregate with heterozygosity for a frameshift variant in the fifth and last exon of the repressor element 1-silencing transcription factor gene (REST). Here, we report the first Italian family in which JS was diagnosed in the proband, a 38-year-old woman, and in her mother. Exome Sequencing identified in both, but not in clinically unaffected members of the family (i.e., a sister and the brother of the proband), the heterozygous pathogenic variant c.2645T>G (p.Leu882*) in exon-5 of the REST gene. This study confirms that exon-5 REST variants cause JS.