Novel variant p.E269K confirms causative role of PLS1 mutations in autosomal dominant hearing loss

• Published in: Clinical genetics Vol. 96; no. 6; pp. 575 - 578
• Main Authors: Diaz‐Horta, Oscar, Bademci, Guney, Tokgoz‐Yilmaz, Suna, Guo, Shengru, Zafeer, Faraz, Sineni, Claire J., Duman, Duygu, Farooq, Amjad, Tekin, Mustafa
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2019
• Subjects: Actin; actin bundling; actin crosslinker; Amino Acid Sequence; Auditory stimuli; Base Sequence; dominant; Family; Female; fimbrin; Genes, Dominant; Hearing loss; Hearing Loss - genetics; Humans; Male; Mechanical stimuli; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - genetics; Microfilament Proteins - chemistry; Microfilament Proteins - genetics; Mutant Proteins - chemistry; Mutation; Mutation - genetics; Pedigree; plastin 1; Turkey; Turkey; plastin 1; actin crosslinker; fimbrin; actin bundling; hearing loss; dominant
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.13626

Auditory reception relies on the perception of mechanical stimuli by stereocilia and its conversion to electrochemical signal. Mechanosensory stereocilia are abundant in actin, which provides them with structural conformity necessary for perception of auditory stimuli. Out of three major classes of actin‐bundling proteins, plastin 1 encoded by PLS1, is highly expressed in stereocilia and is necessary for their regular maintenance. A missense PLS1 variant associated with autosomal dominant hearing loss (HL) in a small family has recently been reported. Here, we present another PLS1 missense variant, c.805G > A (p.E269K), in a Turkish family with autosomal dominant non‐syndromic HL confirming the causative role of PLS1 mutations in HL. We propose that HL due to the p.E269K variant is from the loss of a stable PLS1‐ACTB interaction. Variant p.E269K in PLS1 causing hearing loss.