Genetics and meta-analysis of recessive non-syndromic hearing impairment and Usher syndrome in Maghreb population: lessons from the past, contemporary actualities and future challenges

• Published in: Human genetics 2022-04, Vol.141 (3-4), p.583-593
• Main Authors: Souissi, Amal, Gibriel, Abdullah A., Masmoudi, Saber
• Format: Article
• Language: English
• Subjects: Analysis; Biomedical and Life Sciences; Biomedicine; Consanguinity; Database searching; Gene Function; Hearing loss; Heredity; Human Genetics; Internet/Web search services; Meta-analysis; Metabolic Diseases; Molecular Medicine; Next-generation sequencing; Online databases; Online searching; Population genetics; Review; Social aspects; Social behavior; The Molecular Genetics of Hearing and Deafness
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-021-02314-y

Hereditary hearing impairment (HI) is a heterogeneous condition with over 130 genes associated with genetic non-syndromic HI (NSHI) and Usher syndrome (USH). Approximately 80% of hereditary NSHI cases have autosomal recessive (AR) mode of inheritance. The high rate of consanguinity and endogamy in the Maghreb countries, including Tunisia, Algeria and Morocco, represents a major contributing factor to the development of ARHI. Since the 90s, those populations, with their particular large familiar structure, represented an effective key towards the discovery of the first HI loci and genes. In this study, we performed a deep literature database search to analyze the mutational spectrum and the distribution of pathogenic variants responsible of USH and the NSHI among those populations. To date, 124 pathogenic variants were identified in 32 genes of which over 70% represent population-specific variants. The particular variants’ distribution is related to the high rate of consanguinity as well as the multiple shared features such as demographic history of migrations and social behavior that promoted the spreading of several founder mutations within those countries. This is the first study to report lessons from the past and current actualities of HI within the three Maghreb countries. However, despite the great impact placed by such population for the HI genetic studies, only a few next-generation sequencing platforms have so far been implemented with those countries. We, therefore, believe that those countries should be supported to implement this technology that would definitely be of great value in the discovery of additional novel HI genes/variants.