RESEARCH LETTER Absence of COCH Gene Mutations in Patients With Superior Semicircular Canal Dehiscence Miguel A. Crovetto, 1 Jaime Whyte, 2 Esther Sarasola, 3 Jose A. Rodriguez, 4 and Mar  ıa J. Garc  ıa-Barcina 3 * 1 Department of Otolaryngology, Basurto University Hospital (OSAKIDETZA/Servicio Vasco de Salud), University of the Basque Country (UPV/EHU), Bilbao, Spain 2 Department of Human Anatomy and Histology, Faculty of Medicine, University of Zaragoza, Zaragoza, Spain 3 Department of Genetics, Basurto University Hospital (OSAKIDETZA/Servicio Vasco de Salud), Bilbao, Spain 4 Department of Genetics, Physical Anthropology and Animal Physiology. University of the Basque Country (UPV/EHU), Bilbao, Spain Received 23 September 2011; Accepted 17 October 2011 TO THE EDITOR: Hearing loss has been classically classified as conductive, when the defect is located in the outer and/or middle ear, sensorineural, when the defect is located in the inner ear, or mixed when a combination of both conductive and sensorineural defects occurs. It has been shown, however, that conductive or mixed hearing loss may also result from the alteration of fluid mechanics in the inner ear, as it occurs in labyrinthine fistulae [Minor, 2003], in X-linked deafness Type III/DFNX2 caused by mutations in the POU class 3 homeobox 4(POU3F4) gene [Phelps et al., 1991; Vore et al., 2005], in a small percentage of cases of Pendred syndrome/DFNB4 caused by solute carrier family 26, member 4 (SLC26A4) gene mutation [Campbell et al., 2001; Santos et al., 2010], and in superior semicircular canal dehiscence (SSCD) [Minor et al., 1998; Minor, 2003]. SSCD is a rare disorder originally described by Minor et al. in 1998. In SSCD, the absence of bone overlying the superior semicircular canal creates a third labyrinthine window, leading to loss of acoustic energy and abnormal stimulation of the vestibular system. Besides variable conductive or mixed hearing loss [Chi et al., 2010], the clinical manifestations of SSCD include vertigo induced by loud sounds (Tullio phenomenon), by Valsalva maneuvers, and by exercise. It is important to note that, if detected, SSCD can be partially or fully corrected with surgery [Minor et al., 1998; Crovetto et al., 2008]. The incidence of SSCD is 0.5% [Crovetto et al., 2010]. Given this low incidence, it is not surprising that the etiology of SSCD remains poorly characterized. Interestingly, several studies have recently provided evidence for a possible contribution of genetic alterations to SSCD. Thus, targeted disruption of the Brn4/POU3F4 gene in mice causes abnormal development of the superior semicircular canal, suggesting that mutations in human POU3F4, which cause DFNX2, might be related to SSCD [Sobol and Teng, 2005]. Moreover, in humans, SSCD is sometimes associated to Pendred syndrome [Brandolini and Modugno, 2011]. A possible role for genetic factors in SSCD has been further reinforced by the recent finding of a patient with SSCD in a family with autosomal dominant nonsyndromic hearing loss caused by mutation in the cochlin (COCH) gene [Hildebrand et al., 2009]. In order to evaluate the possibility that mutations in loci responsible for different types of genetic hearing loss are commonly associated with SSCD, we carried out a detailed mutational analysis of the COCH, POU3F4, and SLC26A4 genes in three patients with proven SSCD. Patient 1 is a 43-year-old male reporting a 2-year history of Tullio phenomenon in his right ear, pressure-induced vertigo, oscillopsia, and autophony. Besides this audiovestibular problem, the patient was a healthy man with neither a family history of deafness or vertigo nor any signs suggesting a syndromic deafness. High- resolution temporal bone CT scan showed a dehiscence of the right superior semicircular canal. The patient was operated by trans- mastoid approach to access the canal dehiscence and perform a resurfacing. Currently, he shows a partial relief of vestibular symptoms. Patient 2 is a 58-year-old man reporting a 4-year history of pressure-induced vertigo, oscillopsia, and right autophony. He also suffered from transmission hearing loss. The patient, a heavy smoker, had no personal or family history of audiological or vestibular interest other than the problems mentioned. He did *Correspondence to: Mar  ıa J. Garc  ıa-Barcina, M.D., Department of Genetics, Basurto University Hospital (OSAKIDETZA/Servicio Vasco de Salud), Avenida de Montevideo 18, Bilbao, Spain. E-mail: mariajesus.garciabarcina@osakidetza.net Published online 2 December 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ajmg.a.34377 How to Cite this Article: Crovetto MA, Whyte J, Sarasola E, Rodriguez JA, Garc  ıa-Barcina MJ. 2012. Absence of COCH gene mutations in patients with superior semicircular canal dehiscence. Am J Med Genet Part A 158A:251–253. Ó 2011 Wiley Periodicals, Inc. 251