Clin Genet 2009: 76: 458 – 464 Printed in Singapore. All rights reserved  2009 John Wiley & Sons A/S CLINICAL GENETICS doi: 10.1111/j.1399-0004.2009.01276.x Short Report Chromosome imbalances in syndromic hearing loss Catelani ALPM, Krepischi ACV, Kim CA, Kok F, Otto PA, Auricchio MTBM, Mazzeu JF, Uehara DT, Costa SS, Knijnenburg J, Tabith Jr A, Vianna-Morgante AM, Mingroni-Netto RC, Rosenberg C. Chromosome imbalances in syndromic hearing loss. Clin Genet 2009: 76: 458–464.  John Wiley & Sons A/S, 2009 The cause of hearing impairment has not been elucidated in a large proportion of patients. We screened by 1-Mb array-based comparative genomic hybridization (aCGH) 29 individuals with syndromic hearing impairment whose clinical features were not typical of known disorders. Rare chromosomal copy number changes were detected in eight patients, four de novo imbalances and four inherited from a normal parent. The de novo alterations define candidate chromosome segments likely to harbor dosage-sensitive genes related to hearing impairment, namely 1q23.3–q25.2, 2q22q23, 6p25.3 and 11q13.2–q13.4. The rare imbalances also present in normal parents might be casually associated with hearing impairment, but its role as a predisposition gene remains a possibility. Our results show that syndromic deafness is frequently associated with chromosome microimbalances (14–27%), and the use of aCGH for defining disease etiology is recommended. ALPM Catelani a,b* , ACV Krepischi a,c* , CA Kim d ,F Kok a,e , PA Otto a , MTBM Auricchio a , JF Mazzeu a , DT Uehara a , SS Costa a , J Knijnenburg f , A Tabith Jr g , AM Vianna-Morgante a , RC Mingroni-Netto a and C Rosenberg a,c a Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of S ˜ ao Paulo, Brazil, b Fleury Medicine and Heath, S ˜ ao Paulo, Brazil, c A.C. Camargo Hospital, S˜ ao Paulo, Brazil, d Clinical Genetics Unit, Instituto da Crianc ¸ a, Hospital das Cl´ ınicas, University of S ˜ ao Paulo, Brazil, e Department of Neurology, Hospital das Cl´ ınicas, University of S ˜ ao Paulo, Brazil, f Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands, and g Division of Education and Rehabilitation of Communication Disorders (DERDIC) of the Catholic University of S ˜ ao Paulo (PUC-S ˜ ao Paulo), Brazil * Both authors have contributed equally to this work. Key words: array-CGH – chromosome imbalance – chromosome rearrangement – hearing loss Corresponding author: Carla Rosenberg, PhD, Departamento de Gen ´ etica e Biologia Evolutiva, Instituto de Bioci ˆ encias, Universidade de S ˜ ao Paulo, 05422-970 S˜ ao Paulo, SP, Brazil. Tel.: 55 11 3091 7591; fax: 55 11 3091 7553; e-mail: carlarosenberg@uol.com.br Received 16 February 2009, revised and accepted for publication 14 July 2009 458