X-Linked Hearing Loss: Two Gene Mutation Examples Provide Generalizable Implications for Clinical Care Purpose To describe the inheritance patterns and auditory phenotype features of 3 Canadian families with mutations in 2 X-linked “deafness” genes (DFNX). Method Audiological, medical, and family histories were collected and family members interviewed to compare hearing thresholds and case histories between cases with mutations in SMPX versus ... Research Article
Research Article  |   June 01, 2014
X-Linked Hearing Loss: Two Gene Mutation Examples Provide Generalizable Implications for Clinical Care
 
Author Affiliations & Notes
  • Susan G. Stanton
    Western University, Ontario, Canada
  • Anne Griffin
    Memorial University of Newfoundland, Canada
  • Tracy L. Stockley
    Hospital for Sick Children, Toronto, Ontario, Canada, and University of Toronto, Ontario, Canada
  • Christine Brown
    Western University, Ontario, Canada
  • Terry-Lynn Young
    Memorial University of Newfoundland, Canada
  • Tammy Benteau
    Memorial University of Newfoundland, Canada
  • Nelly Abdelfatah
    Memorial University of Newfoundland, Canada
  • Disclosure: The authors have declared that no competing interests existed at the time of publication.
    Disclosure: The authors have declared that no competing interests existed at the time of publication.×
  • Correspondence to Susan G. Stanton: stanton@nca.uwo.ca
  • Tracy L. Stockley is currently at the University Health Network, Toronto, Ontario, Canada.
    Tracy L. Stockley is currently at the University Health Network, Toronto, Ontario, Canada.×
  • Editor: Larry Humes
    Editor: Larry Humes×
Article Information
Hearing Disorders / Special Populations / Genetic & Congenital Disorders / Research Articles
Research Article   |   June 01, 2014
X-Linked Hearing Loss: Two Gene Mutation Examples Provide Generalizable Implications for Clinical Care
American Journal of Audiology, June 2014, Vol. 23, 190-200. doi:10.1044/2014_AJA-13-0040
History: Received August 9, 2013 , Revised January 22, 2014 , Accepted February 21, 2014
 
American Journal of Audiology, June 2014, Vol. 23, 190-200. doi:10.1044/2014_AJA-13-0040
History: Received August 9, 2013; Revised January 22, 2014; Accepted February 21, 2014
Web of Science® Times Cited: 4

Purpose To describe the inheritance patterns and auditory phenotype features of 3 Canadian families with mutations in 2 X-linked “deafness” genes (DFNX).

Method Audiological, medical, and family histories were collected and family members interviewed to compare hearing thresholds and case histories between cases with mutations in SMPX versus POU3F4.

Results The family pedigrees reveal characteristic X-linked inheritance patterns. Phenotypic features associated with the SMPX (DFNX4) mutation include early onset in males with rapid progression from mild and flat to sloping sensorineural loss, with highly variable onset and hearing loss severity in females. In contrast, phenotypic features associated with the POU3F4 (DFNX2) mutation are characterized by an early onset, mixed hearing loss with fluctuation in males, and a normal hearing phenotype reported for females.

Conclusions The study shows how this unique inheritance pattern and both gender and mutation-specific phenotype variations can alert audiologists to the presence of X-linked genetic etiologies in their clinical practice. By incorporating this knowledge into clinical decision making, audiologists can facilitate the early identification of X-linked hearing loss and contribute to the effective team management of affected families.

Acknowledgments
This research was supported by the Hearing Foundation of Canada Grant R4183A01 to Susan G. Stanton and Tracy L. Stockley; Canadian Foundation for Innovation (New Investigator Award 9384; Leaders Opportunity Fund 13120) and Genome Canada (Atlantic Medical Genetics and Genomics Initiative) to Terry-Lynn Young; and the CIHR-Regional Partnership Program Fellowship (207716/207696) to Nelly Abdelfatah. We gratefully acknowledge support from the National Centre for Audiology, Western University, and financial support from the Janeway Children's Hospital Foundation.
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