Contents lists available at ScienceDirect International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl Genetic heterogeneity of congenital hearing impairment in Algerians from the Ghardaïa province Sonia Talbi a , Crystel Bonnet b , Zied Riahi b , Farid Boudjenah c,d , Malika Dahmani a , Jean-Pierre Hardelin b , Fabienne Wong Jun Tai b , Malek Louha e , Fatima Ammar-Khodja a , Christine Petit b,f,* a Equipe de Génétique, Laboratoire de Biologie Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumédiène, Algiers, Algeria b Inserm UMRS 1120 /Institut Pasteur/Sorbonne University, Paris, France c ENT Department, Frantz Fanon Hospital, Bejaia, Algeria d ENT Department, Sidi Belloua Hospital, Tizi-Ouzou, Algeria e Biochemistry Department, APHP - Armand Trousseau Hospital, Paris, France f Collège de France, Paris, France ARTICLE INFO Keywords: Genetic heterogeneity Hearing impairment Consanguinity Algeria ABSTRACT Background: Consanguinity rate is high in Algeria, and the population is thus at high risk for genetic diseases transmitted on an autosomal recessive mode. Inherited congenital hearing impairment (HI) is a highly hetero- geneous disorder, which affects approximately 1 in 800 Algerian newborns. Several hundreds of genes re- sponsible for deafness have been reported among which more than one hundred are responsible for isolated deafness, of which 19 have already been reported to be involved in the Algerian population. This study focuses on patients from the Ghardaïa province, an ethnically and geographically isolated region of Southern Algeria that has the highest consanguinity rate in the country (56%). Methods: Eleven families, with at least two related members experiencing moderate to profound congenital HI, were recruited and screened for mutations in known HI genes. Results: A preliminary screening for common mutations in GJB2 and GJB6 identified the prevalent GJB2:c.35delG mutation in four families. Targeted exome sequencing further identified the causal mutations in the remaining seven families: CIB2:c.97C > T; p.(Arg33*), MYO7A:c.470+1G > A; p.(?), and SLC26A4:c.410C > T; p.(Ser137Leu) biallelic mutations in two families each, and a TECTA:c.2743 A > G; p. (Ile915Val) monoallelic mutation in the only family with autosomal dominant transmission of the HI. Of note, the missense mutations of SLC26A4 and TECTA had not been previously reported. Conclusion: These results further substantiate the genetic heterogeneity of HI, even in reportedly isolated po- pulations. However, several families may harbor the same mutations as a result of a long history of marriages between relatives. This study has important implications for the HI molecular diagnosis strategy, and to develop genetic counseling for families originating from the Ghardaïa province of Algeria. 1. Introduction Maghrebian populations of North African countries are a mixture of Berbers, Arabs, and Europeans [1,2]. They form distinct human groups that can differ by the territory, language, local customs, and traditions [3,4]. This contributes to the high rate of consanguinity and endogamy, which is a major contributing factor to the manifestation of autosomal recessive disorders, such as congenital (prelingual) hearing impairment (HI) [5,6]. Algeria and Tunisia show the highest prevalence of consanguinity (20–29%) among Maghrebian countries [7]. To date, more than 100 different causal mutations in a total of 32 HI genes have been reported in North Africa [8]. Mutations of GJB2 are the most frequently involved in Algeria (48%) [9], Tunisia (39%) [10], and Morocco (37%) [11]. In addition, some recurrent mutations, such as the founder mutations LRTOMT: c.208C > T and SLC26A4:c.1334 T > G, are most prevalent in Morocco and Tunisia, respectively [8]. In Algeria, 37 different causal mutations have already been identified in a total of 18 genes different from GJB2, in keeping with the genetic heterogeneity https://doi.org/10.1016/j.ijporl.2018.06.012 Received 29 March 2018; Received in revised form 7 June 2018; Accepted 8 June 2018 * Corresponding author. Inserm UMRS 1120 /Institut Pasteur/Sorbonne University, Paris, France. E-mail address: christine.petit@pasteur.fr (C. Petit). International Journal of Pediatric Otorhinolaryngology 112 (2018) 1–5 Available online 12 June 2018 0165-5876/ © 2018 Published by Elsevier B.V. T