Molecular analysis of the TMPRSS3 gene in Moroccan families with non-syndromic hearing loss Majida Charif a , Omar Abidi a , Redouane Boulouiz a , Halima Nahili a , Hassan Rouba a , Mostafa Kandil b , Benjamin Delprat c , Guy Lenaers c , Abdelhamid Barakat a,⇑ a Laboratoire de Génétique Moléculaire et Humaine, Département de Recherche Scientifique, Institut Pasteur du Maroc, 20360 Casablanca, Morocco b Laboratoire des Sciences Anthropogénétiques et Pathologiques, Faculté des Sciences, El jadida, Morocco c Institut des Neurosciences de Montpellier, Université Montpellier Sud de France, U1051, CHU St. Eloi, 80 rue Augustin Fliche, BP 74103, Montpellier Cedex 5, France article info Article history: Received 9 February 2012 Available online 20 February 2012 Keywords: Hearing loss TMPRSS3 gene Polymorphism Moroccan population abstract Autosomal recessive nonsyndromic hearing impairment (ARNSHI) is the most common type of inherited hearing impairment, accounting for approximately 80% of inherited prelingual hearing impairment. Hearing loss is noted to be both phenotypically and genetically heterogeneous. Mutations in the TMPRSS3 gene, which encodes a transmembrane serine protease, are known to cause autosomal recessive non-syndromic hearing impairment DFNB8/10. In order to elucidate if the TMPRSS3 gene is responsible for ARNSHI in 80 Moroccan families with nonsyndromic hearing impairment, the gene was sequenced using DNA samples from these families. Nineteen TMPRSS3 variants were found, nine are located in the exons among which six are missense and three are synonymous. The 10 remaining variations are located in non-coding regions. Missense vari- ants analysis show that they do not have a significant pathogenic effect on protein while pathogenicity of some variant remains under discussion. Thus we show that the TMPRSS3 gene is not a major contributor to non-syndromic deafness in the Moroccan population. Ó 2012 Elsevier Inc. All rights reserved. 1. Introduction Hereditary hearing loss is a common genetic disorder account- ing for at least 60% of prelingual deafness in children. Most cases (70%) are nonsyndromic and are not associated with other signs or symptoms [1,2], while the remaining 30% are syndromic and thus accompany other symptoms and/or signs [3]. The most com- mon pattern of inheritance for nonsyndromic sensorineural hear- ing impairment (NSHI) is autosomal recessive, which accounts for 75–85% of cases and resulting from single gene mutations or from a combination of mutations in different genes, rendering the identification of causative genes and mutations very challeng- ing [4]. To date, 57 non-syndromic deafness genes and more than 1000 discrete deafness-causing mutations have been described (http:// deafnessvariationdatabase.org). Most of them are involved in the inner ear development or functionality, and their mutations gener- ally affect the process of the sound elaboration. Mutations in the TMPRSS3 (MIM 605511), which encodes a transmembrane serine protease have been identified in two forms of hereditary nonsyndromic recessive deafness, DFNB8 and DFNB10 [5,6]. TMPRSS3 belongs to a subfamily of type II transmem- brane serine proteases, which also includes TMPRSS1, TMPRSS2, TMPRSS4 TMPRSS4, TMPRSS5, MSPL and Enteropeptidase [7]. Like the other members of this family, TMPRSS3 is structurally defined by a transmembrane domain located near the amino terminus, a low density lipoprotein receptor A domain (LDLRA) which binds calcium [8] and low density lipoprotein [9], a scavenger receptor cysteine rich domain (SRCR) that is involved in protein–protein interactions [10] and a carboxy terminal serine protease domain (SP) from the S1 family of the SA clan of serine-type peptidases for which the prototype is chymotrypsin [11]. The TMPRSS3 gene, spanning approximately 24 kb on chromosome 21, contains 13 re- ported exons with the initiating codon in exon 2 [12]. In human, there are four alternatively spliced transcripts (TMPRSS3 a, b, c and d), encoding predicted polypeptides of 454, 327, 327 and 344 amino acids, respectively [12]. Sixteen different TMPRSS3 missense mutations that lie in all functional domains have been described to date and were found to disrupt the proteolytic activity of TMPRSS3 [13] although they affect the different functional domains of the protein [12,14–17]. 0006-291X/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.bbrc.2012.02.066 ⇑ Corresponding author. Address: Laboratoire de Génétique Moléculaire et Humaine, Département de Recherche Scientifique, Institut Pasteur du Maroc, 1, Place Louis Pasteur, C.P. 20360 Casablanca, Morocco. Fax: +212 522 26 09 57. E-mail address: hamid.barakat@pasteur.ma (A. Barakat). Biochemical and Biophysical Research Communications 419 (2012) 643–647 Contents lists available at SciVerse ScienceDirect Biochemical and Biophysical Research Communications journal homepage: www.elsevier.com/locate/ybbrc