Ethnic-specific differences in minor allele frequency impact variant categorization for genetic screening of nonsyndromic hearing loss (NSHL) and other genetic disorders. We sought to evaluate all previously reported pathogenic NSHL variants in the context of a large number of controls from ethnically distinct populations sequenced with orthogonal massively parallel sequencing methods. We used HGMD, ClinVar, and dbSNP to generate a comprehensive list of reported pathogenic NSHL variants and re-evaluated these variants in the context of 8,595 individuals from 12 populations and 6 ethnically distinct major human evolutionary phylogenetic groups from three sources (Exome Variant Server, 1000 Genomes project, and a control set of individuals created for this study, the OtoDB). Of the 2,197 reported pathogenic deafness variants, 325 (14.8%) were present in at least one of the 8,595 controls, indicating a minor allele frequency (MAF) > 0.00006. MAFs ranged as high as 0.72, a level incompatible with pathogenicity for a fully penetrant disease like NSHL. Based on these data, we established MAF thresholds of 0.005 for autosomal-recessive variants (excluding specific variants in GJB2) and 0.0005 for autosomal-dominant variants. Using these thresholds, we recategorized 93 (4.2%) of reported pathogenic variants as benign. Our data show that evaluation of reported pathogenic deafness variants using variant MAFs from multiple distinct ethnicities and sequenced by orthogonal methods provides a powerful filter for determining pathogenicity. The proposed MAF thresholds will facilitate clinical interpretation of variants identified in genetic testing for NSHL. All data are publicly available to facilitate interpretation of genetic variants causing deafness.

The aim of this study was to delineate the precise relationship between the sphenoid sinus and internal carotid artery and the optic nerve, as well as to assess incidence of the anatomic variations of these structures. A review of 92 paranasal sinus tomographic scans was made for anatomic variations of the sphenoid sinus and related bony and neurovascular structures. Coronal and axial tomographic sections were obtained with 2.5-mm section thickness. We assessed the protrusion of the internal carotid artery (ICA) and the optic nerve (ON) into the sphenoid sinus, bone dehiscence of these structures, and pneumatization of the anterior clinoid process (ACP) and pterygoid recess (PR), as well as the variations of the sphenoid sinus septum. The protrusion of the ICA into the sphenoid sinus was found in 24 (26.1%) patients. An ON protrusion was present in 29 (31.5%) patients. Pneumatization of the PR was encountered in 27 (29.3%) patients. There was not a statistically significant relationship between the pneumatization of the PR and ICA protrusion into the sphenoid sinus (chi2 = 0.258, p = 0.168). A significant relationship between the ACP pneumatization and protrusion of the ON into the sphenoid sinus was found (chi2= 0.481,p = 0.007). Preoperative recognition of the anatomic variations by the radiologist is beneficial for identification of the limits of dissection. This is particularly important in the sphenoid sinus area where extensive pneumatization of the skull base bones may distort the anatomic configuration. Therefore, axial and coronal CT sections should always be obtained prior to any surgery in the sphenoid sinus area.

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Incudostapedial rebridging ossiculoplasty with bone cement is a cost-effective and safe procedure that yields good hearing results in selected patients.

Bone cement ossiculoplasty offers cost effective and significant improvement in conductive hearing loss.