Characterization of a homozygous nonsense mutation in SLITRK6 associated with sensorineural hearing loss
Date of Award
© 2013 Eric A. Sherman. All rights reserved. Access to this work is restricted to users within the Swarthmore College network and may only be used for non-commercial, educational, and research purposes. Sharing with users outside of the Swarthmore College network is expressly prohibited. For all other uses, including reproduction and distribution, please contact the copyright holder.
Bachelor of Arts
John B. Jenkins
Elizabeth Ann Vallen
Four children from a single Old Order Amish family presented with congenital hearing loss. Hearing tests revealed auditory neuropathy, indicating that these children suffer from sensorineural hearing loss, a defect in the neural connections of the inner ear. In an effort to identify the genetic basis of this disease, a genome-wide mapping study was performed using Affymetrix 10K single nucleotide polymorphism (SNP) arrays. After Sanger sequencing of candidate genes, a novel nonsense mutation in SLITRK6 (c.1240C>T, p.Glu4l4Ter) was found to be homozygous in all patients. Functional studies of this variant confirmed the premature truncation of the SLITRK6 protein. Secondary to this truncation, SLITRK6 localizes to the cytosol rather than its native location in the plasma membrane. While the precise biochemical duties of SLITRK6 are unknown, such a dramatic error in protein structure and localization likely results in a null allele. Future studies designed to investigate the specific biochemical interactions observed in wild type SLITRK6 may further detail the auditory defects observed in these children, ultimately providing insights into treatments for SLITRK6-induced sensorineural hearing loss.
Sherman, Eric A. , '13, "Characterization of a homozygous nonsense mutation in SLITRK6 associated with sensorineural hearing loss" (2013). Senior Theses, Projects, and Awards. 128.