A Novel Candidate Gene MACF1 is Associated with Autosomal Dominant Non-syndromic Hearing Loss in an Iranian Family

Abstract

Cytoskeletal dynamics, the interplay of actin, microtubules, and septins, is a highly coordinated and tightly regulated process. Defects in the proteins involved can result in a wide range of cellular consequences. Hearing loss is the most common sensory defect and exhibits extraordinary genetic and phenotypic heterogeneity. Currently, there are more than 170 genes casually linked to non-syndromic hearing loss (NSHL), of which more than 60 are associated with autosomal dominant inheritance. Here, we add to this growing number by implicating MACF1 (OMIM # 608271), as a novel candidate gene for autosomal dominant non-syndromic hearing loss (ADNSHL). MACF1’s cytoskeleton integrator function and hair cell expression pattern lead one to believe that it is a necessary protein for hair cells. Many protein domains in MACF1 allow for dynamic interaction with the cytoskeleton. A large Iranian family segregating progressive ADNSHL was recruited for this study. The proband had bilateral mild-moderate sensorineural hearing loss and was negative for GJB2 mutations. After applying exome sequencing on the proband, a missense mutation c.1378C>T (p.His460Tyr) was found in MACF1 and co-segregated with the hearing loss in the extended family. We speculated that MACF1 mutations probably cause non-syndromic hearing loss inherited in an autosomal dominant manner. The potential functional impact of the identified variant will be investigated through further analysis.

Keywords: Autosomal dominant non-syndromic hearing loss, Iran, MACF1, Novel gene