biostudies-literatureUnknown109(1)Lodato VEU-NextGenerationJones 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.Clinical genetics199-203https://www.ebi.ac.uk/biostudies/studies/S-EPMC12674978biostudies-literatureNovel Pathogenic Variant Confirms the Association of REST and Jones Syndrome.PMC12674978Grammatico PTurchetta RPalmisano BRiminucci MCelli LAllegra ELodato VColizza ABianco MRStanganelli FRFGalli MCorsi ABottillo IMessineo DD'Angeli GGianno FfalseNovel Pathogenic Variant Confirms the Association of REST and Jones Syndrome.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.2026-01-01T00:00:00Z2026 Jan2026-06-05T22:18:07.491Z2026-05-22T03:15:23.185ZS-EPMC126749784060539810.1111/cge.70017