Novel pathogenic mutations and further evidence for clinical relevance of genes and variants causing hearing impairment in Tunisian population

Souissi, Amal; Said, Mariem Ben; Ayed, Ikhlas Ben; Elloumi, Inés; Bouzid, Amal; Mosrati, Mohamed Ali; Hasnaoui, Mehdi; Belcadhi, M; Idriss, Nabil; Kamoun, Hassen; Gharbi, Nourhene; Gibriel, Abdullah Ahmed; Tlili, Abdelaziz; Masmoudi, Saber

doi:10.1016/j.jare.2021.01.005

Cited by 20 publications

(17 citation statements)

References 64 publications

(42 reference statements)

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“…Various molecular diagnostic techniques such as RFLP, Sanger sequencing and microarray have been widely utilized in detecting several HL mutations ( Gibriel et al, 2019 , Chakchouk et al, 2015 ). However, addressing such complexity necessitates the use of sophisticated NGS platforms for identification of causative HL mutations rapidly and efficiently ( Souissi et al, 2021 , Ben Ayed et al, 2021 ). In this study, we investigated a consanguineous Emirati family affected with NSHL.…”

Section: Discussionmentioning

confidence: 99%

“…Although traditional approaches have led to great insights into the underlying genetic causes of NSHL, the advent of next generation sequencing (NGS) has expedited the discovery of novel NSHL genes and mutations ( Souissi et al, 2021 ). In fact, NGS-based platforms have been involved in the identification of more than 40% of NSHL genes known today ( https://hereditaryhearingloss.org/ ).…”

Section: Introductionmentioning

confidence: 99%

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Whole exome sequencing, in silico and functional studies confirm the association of the GJB2 mutation p.Cys169Tyr with deafness and suggest a role for the TMEM59 gene in the hearing process

Mahfood

Chouchen

Mohamed

et al. 2021

Saudi Journal of Biological Sciences

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The development of next generation sequencing techniques has facilitated the detection of mutations at an unprecedented rate. These efficient tools have been particularly beneficial for extremely heterogeneous disorders such as autosomal recessive non-syndromic hearing loss, the most common form of genetic deafness. GJB2 mutations are the most common cause of hereditary hearing loss. Amongst them the NM_004004.5: c.506G > A (p.Cys169Tyr) mutation has been associated with varying severity of hearing loss with unclear segregation patterns. In this study, we report a large consanguineous Emirati family with severe to profound hearing loss fully segregating the GJB2 missense mutation p.Cys169Tyr. Whole exome sequencing (WES), in silico, splicing and expression analyses ruled out the implication of any other variants and confirmed the implication of the p.Cys169Tyr mutation in this deafness family. We also show preliminary murine expression analysis that suggests a link between the TMEM59 gene and the hearing process. The present study improves our understanding of the molecular pathogenesis of hearing loss. It also emphasizes the significance of combining next generation sequencing approaches and segregation analyses especially in the diagnosis of disorders characterized by complex genetic heterogeneity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Whole exome sequencing, in silico and functional studies confirm the association of the GJB2 mutation p.Cys169Tyr with deafness and suggest a role for the TMEM59 gene in the hearing process

Mahfood

Chouchen

Mohamed

et al. 2021

Saudi Journal of Biological Sciences

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“…Except for a few studies from Cameroon (Trotta et al 2011), Nigeria (Lasisi et al 2014), and South Africa (Bardien et al 2009); the remaining two reports were from North Africa (Table S6). The m.1555A>G variant was the most frequently associated mitochondrial variant found in two out of the three countries, Tunisia (Mkaouar-Rebai et al 2010;Souissi et al 2021) and Morocco (Nahili et al 2010). However, the reported frequencies of m.1555A>G variant were less than 2%, indicating the low contribution of the variant to HI in the studies reviewed.…”

Section: Mitochondrial Dna Variantsmentioning

confidence: 93%

“…Except for connexin genes, 34 NSHI gene variants were identified from 7 countries: Algeria (Behlouli et al 2016;Talbi et al 2018), Cameroon (Lebeko et al 2016;Wonkam-Tingang et al 2020b, 2021Wonkam et al 2021a, b), Ghana (Adadey et al 2021), Morocco (Amalou et al 2021;Bakhchane et al 2015a;Ebermann et al 2007), Nigeria (Yan et al 2016), South Africa (Yan et al 2016), Tunisia (Souissi et al 2021;Belguith et al 2009;Bensaid et al 2011;Chakchouk et al 2015;Chiereghin et al 2021;Tlili et al 2005Tlili et al , 2008Masmoudi et al 2001). Tunisia recorded the highest number of NSHI genes with PLP variants (11/34).…”

Section: Non-connexin Nshi Gene Variantsmentioning

confidence: 99%

Hearing loss in Africa: current genetic profile

et al. 2021

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Hearing impairment (HI) is highly heterogeneous with over 123 associated genes reported to date, mostly from studies among Europeans and Asians. Here, we performed a systematic review of literature on the genetic profile of HI in Africa. The study protocol was registered on PROSPERO, International Prospective Register of Systematic Reviews with the registration number “CRD42021240852”. Literature search was conducted on PubMed, Scopus, Africa-Wide Information, and Web of Science databases. A total of 89 full-text records was selected and retrieved for data extraction and analyses. We found reports from only 17/54 (31.5%) African countries. The majority (61/89; 68.5%) of articles were from North Africa, with few reports found from sub-Saharan Africa. The most common method used in these publications was targeted gene sequencing (n = 66/111; 59.5%), and only 13.5% (n = 15/111) used whole-exome sequencing. More than half of the studies were performed in families segregating HI (n = 51/89). GJB2 was the most investigated gene, with GJB2: p.(R143W) founder variant only reported in Ghana, while GJB2: c.35delG was common in North African countries. Variants in MYO15A were the second frequently reported in both North and Central Africa, followed by ATP6V1B1 only reported from North Africa. Usher syndrome was the main syndromic HI molecularly investigated, with variants in five genes reported: USH2A, USH1G, USH1C, MYO7A, and PCDH15. MYO7A: p.(P1780S) founder variant was reported as the common Usher syndrome variant among Black South Africans. This review provides the most comprehensive data on HI gene variants in the largely under-investigated African populations. Future exomes studies particularly in multiplex families will likely provide opportunities for the discovery of the next sets of novel HI genes, and well as unreported variants in known genes to further our understanding of HI pathobiology, globally.

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“…The same was found at term pregnancy at 24 h. Interestingly, Octn2 mRNA level was not affected [ 119 ]. In contrast, metabolic acidosis induced in rats caused an up-regulation in the kidney Octn1 at both the mRNA and protein level [ 120 ]. Another example is given by inflammation induced by LPS, which inhibits the expression and activity of OCTN1 in alveolar epithelial cells (A549), potentially reducing the distribution of inhaled medicine in pulmonary diseases [ 108 ].…”

Section: Relevance To Human Pathologymentioning

confidence: 99%

OCTN1: A Widely Studied but Still Enigmatic Organic Cation Transporter Linked to Human Pathology and Drug Interactions

Pochini

Galluccio

Scalise

et al. 2022

IJMS

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The Novel Organic Cation Transporter, OCTN1, is the first member of the OCTN subfamily; it belongs to the wider Solute Carrier family SLC22, which counts many members including cation and anion organic transporters. The tertiary structure has not been resolved for any cation organic transporter. The functional role of OCNT1 is still not well assessed despite the many functional studies so far conducted. The lack of a definitive identification of OCTN1 function can be attributed to the different experimental systems and methodologies adopted for studying each of the proposed ligands. Apart from the contradictory data, the international scientific community agrees on a role of OCTN1 in protecting cells and tissues from oxidative and/or inflammatory damage. Moreover, the involvement of this transporter in drug interactions and delivery has been well clarified, even though the exact profile of the transported/interacting molecules is still somehow confusing. Therefore, OCTN1 continues to be a hot topic in terms of its functional role and structure. This review focuses on the most recent advances on OCTN1 in terms of functional aspects, physiological roles, substrate specificity, drug interactions, tissue expression, and relationships with pathology.

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Novel pathogenic mutations and further evidence for clinical relevance of genes and variants causing hearing impairment in Tunisian population

Abstract: Graphical abstract

Cited by 20 publications

References 64 publications

Whole exome sequencing, in silico and functional studies confirm the association of the GJB2 mutation p.Cys169Tyr with deafness and suggest a role for the TMEM59 gene in the hearing process

Whole exome sequencing, in silico and functional studies confirm the association of the GJB2 mutation p.Cys169Tyr with deafness and suggest a role for the TMEM59 gene in the hearing process

Hearing loss in Africa: current genetic profile

OCTN1: A Widely Studied but Still Enigmatic Organic Cation Transporter Linked to Human Pathology and Drug Interactions

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