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

Area of Science:

• Genetics
• Rare Diseases
• Molecular Biology

Background:

• Jones syndrome (JS) is an ultra-rare autosomal dominant disorder.
• JS is characterized by gingival fibromatosis and progressive sensorineural hearing loss.
• Previous research linked JS to the repressor element 1-silencing transcription factor (REST) gene in a Finnish family.

Purpose of the Study:

• To investigate the genetic basis of Jones syndrome in an Italian family.
• To confirm the role of the REST gene in the etiology of JS.

Main Methods:

• Exome sequencing was performed on affected and unaffected family members.
• Segregation analysis of identified variants within the family.

Main Results:

• A heterozygous pathogenic variant (c.2645T>G, p.Leu882*) in exon 5 of the REST gene was identified in the Italian proband and her mother.
• This variant was absent in unaffected family members, confirming co-segregation with JS.
• This finding supports the role of REST gene variants in causing Jones syndrome.

Conclusions:

• The study confirms that heterozygous variants in exon 5 of the REST gene are causative of Jones syndrome.
• This expands the understanding of JS genetics beyond the previously reported Finnish family.
• Identifies a specific pathogenic variant in the REST gene associated with JS.