Audiometric and Vestibular Features in a Second Dutch DFNA20/26 Family with a Novel Mutation inACTG1

Abstract

The audiometric phenotype of the Dutch DFNA20/26 family with a novel mutation in ACTG1 was largely consistent with previous reports on DFNA20/26. Considerable variations were found in audiogram configurations within the family. This is the first known DFNA20/26 family that has experienced tinnitus.

A novel mutation in ACTG1 causing Baraitser-Winter syndrome with extremely variable expressivity in three generations

“…It is located within subdomain 2 within the actin protein and is in close proximity to previously reported pathogenic variants. This variant segregates with the hearing loss in this family, who exhibit hearing loss similar to previously observed DFNA20/26 NSHL 10 . The variant is associated with variable expressivity in the reported family.…”

Mutational Spectrum and Clinical Features of Patients With ACTG1 Mutations Identified by Massively Parallel DNA Sequencing

“…9 However, the patients in our cohort experienced tinnitus regardless of subdomain (the mutations identified in this study were located in the various subdomains, 2974; subdomain 2, JHLB964; subdomain 1, 3070; subdomain 1, 3837: subdomain 3), indicating that tinnitus is not a subdomain-specific symptom but is associated with the severity of hearing loss. 9 However, the patients in our cohort experienced tinnitus regardless of subdomain (the mutations identified in this study were located in the various subdomains, 2974; subdomain 2, JHLB964; subdomain 1, 3070; subdomain 1, 3837: subdomain 3), indicating that tinnitus is not a subdomain-specific symptom but is associated with the severity of hearing loss.…”

Actin in hair cells and hearing loss

“…Genes in the 2.4-Mb DFNA20/26 interval were screened by DNA sequencing, and a missense mutation (p.T89I) that substitutes an isoleucine for the wild-type threonine at residue 89 of ACTG1 was found to co-segregate with deafness in this family (Zhu et al, 2003). Nine additional missense mutations of ACTG1 have been identified, each of which has been reported in just one family (van Wijk et al, 2003; Zhu et al, 2003; Rendtorff et al, 2006; Liu et al, 2008; de Heer et al, 2009; Morin et al, 2009). …”

“…Four are muscle-specific ( ACTA1 , ACTC1 , ACTA2 , and ACTG2 ) and two encode β and γ cytoplasmic actins ( ACTB , ACTG1 ). Mutations of human β-actin are associated with syndromes that include deafness as a significant feature (Nunoi et al, 1999; Procaccio et al, 2006; Riviere et al, 2011) while mutant alleles of γ-actin cause syndromic and non-syndromic progressive hearing loss (van Wijk et al, 2003; Zhu et al, 2003; Rendtorff et al, 2006; Liu et al, 2008; de Heer et al, 2009; Morin et al, 2009; Riviere et al, 2011). Despite being encoded by six different genes, mammalian actins are 90% identical to one another (reviewed in Khaitlina, 2001).…”