Monogenic nonsyndromic otosclerosis: Audiological and linkage analysis in a large Greek pedigree Vassiliki Iliadou a,1 , Kris Van Den Bogaert b,1 , Nikolaos Eleftheriades a , George Aperis c , Kathleen Vanderstraeten b , Erik Fransen b , Melissa Thys b , Maria Grigoriadou c , Andreas Pampanos c , John Economides d , Theophilos Iliades a , Guy Van Camp b , Michael B. Petersen c, * a Audiology Unit, Department of Otorhinolaryngology, Aristotle University of Thessaloniki, AHEPA Hospital, GR-54006 Thessaloniki, Greece b Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium c Department of Genetics, Institute of Child Health, ‘‘Aghia Sophia’’ Children’s Hospital, GR-11527 Athens, Greece d Department of Audiology-Neurootology, ‘‘Aghia Sophia’’ Children’s Hospital, GR-11527 Athens, Greece Received 2 April 2005; accepted 12 August 2005 International Journal of Pediatric Otorhinolaryngology (2006) 70, 631—637 www.elsevier.com/locate/ijporl KEYWORDS Audiological analysis; Genetic linkage analysis; Monogenic inheritance; Otosclerosis Summary Objective: The aim of our study was to characterize the hearing impairment in a large multigenerational Greek family with autosomal dominant nonsyndromic otosclerosis and to perform genetic linkage analysis to known otosclerosis loci and collagen genes. In addition, we looked for mutations in the NOG gene to rule out congenital stapes ankylosis syndrome. Methods: Audiological analysis of the affected persons was based on multiple linear regression (MLR) analysis and construction of age-related typical audiograms (ARTA). Genotyping of microsatellite DNA polymorphisms for known otosclerosis (OTSC) loci or collagen genes and linkage analysis using the MLINK computer program were per- formed. The coding region of the NOG gene was screened for mutations by direct DNA sequencing. Results: The hearing loss in this family appears in childhood as conductive, but soon becomes mixed. Because the additional sensorineural component is progressive, this finally has lead to a pure sensorineural hearing loss in some family members, as the conductive component is masked. Audiological analysis showed an age-independent * Corresponding author. Tel.: +30 210 7467789; fax: +30 210 7700111. E-mail address: petersen@otenet.gr (M.B. Petersen). 1 The first two authors contributed equally to this work. 0165-5876/$ — see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2005.08.012