Triple-A Syndrome in Morocco: Founder Effect, Age Estimation of the AAAS c.1331+1G>A Variant, and Implications for Genetic Diagnosis.

Introduction: Triple-A syndrome (Triple-A) is an autosomal recessive disorder characterized by alacrimia, achalasia, and adrenal insufficiency. Several variants on the AAAS gene have been described, and some variants are clustered in particular geographical areas, such as the c.1331+1G>A variant which is very frequent in North Africa. Here, we describe the genetic features of Triple-A in a series of unrelated families from Morocco. Methods: Screening for the AAAS c.1331+1G>A variant was performed by direct sequencing or by PCR-RFLP. Haplotype analysis using Single Tandem Repeat (STR) markers flanking AAAS gene was performed in order to evaluate the founder effect and estimate the age of the c.1331+1G>A variant. Results: Seven unrelated families with ten individuals clinically diagnosed with Triple-A were evaluated for sequence variations in the AAAS gene. The median age at diagnosis was 3 years, with a range between 2 and 11 years. Molecular analysis revealed that all patients were homozygous for the c.1331+1G>A variant. This variant was not found in 200 healthy controls, indicating that carriers are very rare in the general Moroccan population. Subsequently, STR marker analysis revealed a founder effect and that the most recent common ancestor of Triple-A patients in Morocco would have lived 125 years ago. Conclusion: This is the largest series of Triple-A in Morocco. The same AAAS c.1331+1G>A variant was found in all patients, suggesting a founder effect in Morocco which was subsequently confirmed by microsatellite marker analysis. Therefore, this variant should be systematically investigated to diagnose Triple-A in Morocco.

First report on chromosomal abnormalities in Eastern Morocco: Identification of a new case of a de novo partial trisomy 13q using single-nucleotide polymorphism array.

BACKGROUND: Chromosomal abnormalities are the main cause of birth defects, intellectual disability, and miscarriages. They contribute to significant human morbidity and infant mortality. Here we report for the first time the chromosomal abnormalities encountered in the population of Eastern Morocco. Furthermore, we describe a new case of a de novo partial trisomy 13q combined with a terminal deletion in an 11-day-old girl. METHODS: From November 2015 to March 2022, 195 patients from the BRO Biobank who were clinically suspected of having chromosomal abnormalities were referred to the cytogenetics laboratory of the Genetics Unit of the Faculty of Medicine and Pharmacy of Oujda for cytogenetic study. Karyotyping analysis was performed on peripheral blood samples using standard R banding techniques. To identify single-nucleotide polymorphism (SNP) and copy number variants (CNVs), Illumina SNP array was used. RESULTS: Among 195 studied cases, 32 (16.4 %) had abnormal karyotypes, of which 12 cases had numerical aberrations while 20 cases had structural aberrations. The most common numerical aberrations were Turner syndrome and Down syndrome followed by Edward, Patau, and Klinefelter syndromes. For structural aberrations, translocations were the most common, followed by derivative chromosomes, inversions, deletions, and an addition on chromosome 13 identified in an 11-day-old girl. To further characterize this addition, SNP array was carried out and revealed a 58.8-Mb duplication in region 13q14.3q34 associated with a 1-Mb deletion in region 13q34. Follow-up parental chromosomes analysis showed normal karyotypes for the parents, confirming that this partial trisomy 13q was de novo. Comparison of the phenotype associated with this novel duplication on chromosome 13q with those previously reported confirmed the considerable variability in the phenotype of the patients with partial trisomy 13q. CONCLUSION: This study provided the first report on chromosomal abnormalities in Eastern Morocco and it enriched the phenotype spectrum of partial trisomy 13q and further confirmed the genotype-phenotype correlations. Furthermore, these findings justify the need to set up microarray comparative genomic hybridization techniques in Morocco for better genetic diagnosis.

A novel variant in BMPR1B causes acromesomelic dysplasia Grebe type in a consanguineous Moroccan family: Expanding the phenotypic and mutational spectrum of acromesomelic dysplasias.

Acromesomelic dysplasia Grebe type (AMD Grebe type) is an autosomal recessive trait characterized by short stature, shortened limbs and malformations of the hands and feet. It is caused by variants in the growth differentiation factor 5 (GDF5) or, in rare cases, its receptor, the bone morphogenetic protein receptor-1B (BMPR1B). Here, we report a novel homozygous BMPR1B variant causing AMD Grebe type in a consanguineous Moroccan family with two affected sibs from BRO Biobank. Remarkably, the affected individuals showed additional features including bilateral simian creases, lumbar hyperlordosis, as well as lower limb length inequality and dislocated hips in one of them, which were never reported previously for AMD Grebe type patients. The identified novel BMPR1B variant (c.1201C>T, p.R401*) is predicted to result in loss of function of the BMPR1B protein either by nonsense-mediated mRNA decay or production of a truncated BMPR1B protein. Thus, these findings expand the phenotypic and mutational spectrum of AMD, and may improve the diagnosis of AMD and enable appropriate genetic counselling to be offered to patients.

Genotype-phenotype correlations in RHOBTB2-associated neurodevelopmental disorders.

PURPOSE: Missense variants clustering in the BTB domain region of RHOBTB2 cause a developmental and epileptic encephalopathy with early-onset seizures and severe intellectual disability. METHODS: By international collaboration, we assembled individuals with pathogenic RHOBTB2 variants and a variable spectrum of neurodevelopmental disorders. By western blotting, we investigated the consequences of missense variants in vitro. RESULTS: In accordance with previous observations, de novo heterozygous missense variants in the BTB domain region led to a severe developmental and epileptic encephalopathy in 16 individuals. Now, we also identified de novo missense variants in the GTPase domain in 6 individuals with apparently more variable neurodevelopmental phenotypes with or without epilepsy. In contrast to variants in the BTB domain region, variants in the GTPase domain do not impair proteasomal degradation of RHOBTB2 in vitro, indicating different functional consequences. Furthermore, we observed biallelic splice-site and truncating variants in 9 families with variable neurodevelopmental phenotypes, indicating that complete loss of RHOBTB2 is pathogenic as well. CONCLUSION: By identifying genotype-phenotype correlations regarding location and consequences of de novo missense variants in RHOBTB2 and by identifying biallelic truncating variants, we further delineate and expand the molecular and clinical spectrum of RHOBTB2-related phenotypes, including both autosomal dominant and recessive neurodevelopmental disorders.

Molecular heterogeneity of ß-thalassemia variants in the Eastern region of Morocco.

BACKGROUND: ß-thalassemia syndromes are the most common hereditary blood disorders in the world and are recognized as a major health problem in Morocco. They are characterized by the reduction or the absence of ß-globin chain synthesis. The severity of the disease depends on the nature of the variants affecting the ß-globin gene (HBB), and each ethnic group has its own mutation spectrum. Hereby, we present, for the first time, the molecular profile of ß-thalassemia in the Eastern region of Morocco. METHODS: This study concerns 39 cases from 33 families who were enrolled in the BRO Biobank. Nineteen were diagnosed with ß-thalassemia major and 20 with ß-thalassemia minor. To detect mutations of the ß-globin gene, we have used RFLP-PCR and Sanger sequencing. RESULTS: Nine known ß-thalassemia variants have been identified. Among these, we reported, for the first time in the Moroccan population, the Czechoslovakian variant C38/39(-C) at homozygous state. The C39(C > T) was the most frequent variant (72.54%), followed by FSC5(-CT) (5.88%), FSC6(-A), IVS-1-110(G > A), -29(A > G), C38/39(-C) (3.92% each), and finally by IVS-I-1(G > A), IVS-II-1(G > A), and -56(G > C) (1.96%). Of particular interest this mutational spectrum of ß-thalassemia is very different from that found in previous studies in Morocco or in other North African countries. CONCLUSION: This study is the first contribution to the description of the molecular profile of ß-thalassemia in the Eastern region of Morocco. It shows the high molecular heterogeneity of ß-thalassemia in our country. Therefore, these results can be valuable for the implementation of carrier screening, genetic counseling, and prenatal diagnosis programs.

Detection of a new deleterious SGCE gene variant in Moroccan family with inherited myoclonus-dystonia.

Myoclonus-dystonia (M-D) is a pleiotropic neuropsychiatric disorder with autosomal dominant mode of inheritance with variable severity and incomplete penetrance. Pathogenic variants in ξ-sarcoglycan gene SGCE are the most frequently known genetic cause of M-D with maternal imprinting, and in most cases, a symptomatic individual inherits the pathogenic variant from his or her father. This work reported a missense mutation c.662G> T inherited in the M-D Moroccan family described for the first time, which is deleterious based on protein modeling analysis.

Morocco's First Biobank: Establishment, Ethical Issues, Biomedical Research Opportunities, and Challenges.

BACKGROUND: Biobanks are highly organized infrastructures that allow the storage of human biological specimens associated with donors' personal and clinical data. These infrastructures play a key role in the development of translational medical research. In this context, we launched, in November 2015, the first biobank in Morocco (BRO Biobank) in order to promote biomedical research and provide opportunities to include Moroccan and North African ethnic groups in international biomedical studies. Here, we present the setup and the sample characteristics of BRO Biobank. METHODS: Patients were recruited at several departments of two major health-care centers in the city of Oujda. Healthy donors were enrolled during blood donation campaigns all over Eastern Morocco. From each participant, personal, clinical, and biomedical data were collected, and several biospecimens were stored. Standard operating procedures have been established in accordance with international guidelines on human biobanks. RESULTS: Between November 2015 and July 2020, 2446 participants were recruited into the BRO Biobank, of whom 2013 were healthy donors, and 433 were patients. For healthy donors, the median age was 35 years with a range between 18 and 65 years and the consanguinity rate was 28.96%. For patients, the median age was 11 years with a range between 1 day and 83 years. Among these patients, 55% had rare diseases (hemoglobinopathies, intellectual disabilities, disorders of sex differentiation, myopathies, etc.), 13% had lung cancer, 4% suffered from hematological neoplasms, 3% were from the kidney transplantation project, and 25% had unknown diagnoses. The BRO Biobank has collected 5092 biospecimens, including blood, white blood cells, plasma, serum, urine, frozen tissue, FFPE tissue, and nucleic acids. A sample quality control has been implemented and suggested that samples of the BRO Biobank are of high quality and therefore suitable for high-throughput nucleic acid analysis. CONCLUSIONS: The BRO Biobank is the largest sample collection in Morocco, and it is ready to provide samples to national and international research projects. Therefore, the BRO Biobank is a valuable resource for advancing translational medical research.

Patients' Knowledge and Attitude Toward Biobanks in Eastern Morocco.

Background: To integrate biobanks into the Moroccan health system and to promote biobanks-based research projects, it is necessary to explore the knowledge of patients, their attitudes toward biobanks, and the reasons that motivate them to participate in biobanks. Methods: Face-to-face interviews were conducted with patients, and data were analyzed using SPSS. Results: One thousand one hundred thirty-three questionnaires were completed. The mean age of patients was 47.74 years (SD 15.26 years). More women (69%) were involved in this survey. Of the respondents, 97% had never heard of the term "biobanks." Knowledge of biobanks varied significantly with respondents' education level. Overall, 80.7% of the participants (n = 914) expressed their willingness to participate in biobanking through donation of biospecimens associated with personnel and health data. Willingness to participate in biobanks was significantly associated with gender and age. We found that the main barriers to participation in biobanks were the lack of trust in biomedical research and concerns about privacy. When asked about the preferred type of consent, the majority of patients (75%) opted for a one-time consent. Conclusion: Despite the lack of knowledge of biobanks among patients in Eastern Morocco, the majority of them expressed willingness to participate in biobanking through donation of biospecimens. However, active participation depended upon a number of factors, notably, the trust in biomedical research and privacy. Therefore, more efforts are needed to increase awareness and promote wider participation in biobanking.

Novel Mutation in AIFM1 Gene Associated with X-Linked Deafness in a Moroccan Family.

INTRODUCTION: Auditory neuropathy is a hearing disorder where outer hair cell function within the cochlea is normal, but inner hair cell and/or the auditory nerve function is disrupted. It is a heterogeneous disorder, which can have either congenital or acquired causes. METHODS: We found a disease-segregating mutation in the X-linked AIFM1 gene through whole-exome sequencing, encoding the apoptosis-inducing factor mitochondrion-associated 1. RESULTS: The impact of the c.1045A>G; p.(Ser349Gly) mutation on the AIFM1 protein was predicted using different bioinformatics tools. The pedigree analysis in the examined family was consistent with X-linked dominant inheritance. DISCUSSION/CONCLUSION: To our knowledge, this is the first study that identifies a mutation in the AIFM1 gene in Moroccan patients suffering from X-linked auditory neuropathy.

[Lung cancer in Eastern Morocco: where do we stand?] / Cancer du poumon au Maroc Oriental: où en sommes-nous?

INTRODUCTION: Lung cancer is the most common cancer in men living Eastern Morocco. We here present the first report on the clinical, pathological and therapeutic features of lung cancer in Eastern Morocco. METHODS: We conducted a retrospective study of 738 patients diagnosed with lung cancer at the Hassan II, Oncology Center between October 2005 and December 2014. RESULTS: Among the cases studied, 671 patients were men and 67 women; 95.01% of men and 1.54% of women were smokers. The average age of patients was 59.1 ± 11.9 years. Most patients (97%) were diagnosed at advanced stage disease. Only 4 out of 227 patients with advanced adenocarcinoma underwent molecular test. In addition, no patient in our series received targeted therapy. In this series, 20.46% of patients had less than 50 years. Compared to patients aged 50 years and older, cannabis consumption was higher (p<0.001) in patients less than 50 years and as well as a higher rate of adenocarcinoma (p<0.01). By contrast, in these patients, tobacco consumption was lower (p<0.001) as well as the rate of squamous cell carcinoma (p<0.01) and small cell cancer (p<0.05). CONCLUSION: Unlike Western countries, in Eastern Morocco lung cancer is diagnosed late, affects younger people and access to molecular tests is still very limited. These results justify the need to implement effective programs against lung cancer as well as to facilitate access to molecular tests and new therapeutic tools in Eastern Morocco.

Cancer incidence in eastern Morocco: cancer patterns and incidence trends, 2005-2012.

BACKGROUND: Cancer is one of the major health problems worldwide. In this article, we present for the first time the cancer incidence trends, the distribution and the socioeconomic profile of incident cancer cases in Eastern Morocco over a period of eight years. METHODS: Retrospective descriptive study of patients diagnosed with cancer at the Hassan II Regional Oncology Center (ROC) since it was created in October 2005 until December 2012. During the study period, the ROC was the only hospital specialized in cancer care in Eastern Morocco. RESULTS: A total of 7872 incident cases of cancer were registered in Eastern Morocco. Among these incident cases 5220 cases were women and 2652 were men, with a female to male ratio of 1.97. The mean age at diagnosis was 58 years for males and 52 for females and 94% of the patients aged over 30 years. For both sexes combined and for all cancer sites, breast cancer was the commonest followed by cervix uteri, colon-rectum, lung, nasopharynx, and stomach cancers. The most common cancer in women was breast cancer, followed respectively by cervix uteri cancer, colon-rectum cancer, ovary cancer, and stomach cancer. In men, the lung cancer ranked first, followed respectively by colon-rectum cancer, nasopharynx cancer, prostate cancer, and stomach cancer. For most cancers, crude incidence rates (CR) have increased significantly. The CR for all cancers combined has increased from 56.6 to 80.3 per 100,000 females and from 32.3 to 42.6 per 100,000 males during the study period. Patients profile analysis showed that 79% of cancer patients were from urban areas, 83% were unemployed and 85% had no health insurance. CONCLUSIONS: The distribution of cancers in Eastern Morocco is different from those observed in other regions of Morocco. Unlike most countries, women were much more affected with cancer than men in Eastern Morocco. More importantly, the rates of many cancers are rising. Therefore, our data justify the need to develop effective programs for cancer control and prevention in Eastern Morocco. A better access to cancer care should be a priority of the health policies, given that the majority of cancer patients in Eastern Morocco are unemployed, and do not have medical care coverage.

Novel compound heterozygous MYO7A mutations in Moroccan families with autosomal recessive non-syndromic hearing loss.

The MYO7A gene encodes a protein belonging to the unconventional myosin super family. Mutations within MYO7A can lead to either non syndromic hearing loss or to the Usher syndrome type 1B (USH1B). Here, we report the results of genetic analyses performed on Moroccan families with autosomal recessive non syndromic hearing loss that identified two families with compound heterozygous MYO7A mutations. Five mutations (c.6025delG, c.6229T>A, c.3500T>A, c.5617C>T and c.4487C>A) were identified in these families, the latter presenting two differently affected branches. Multiple bioinformatics programs and molecular modelling predicted the pathogenic effect of these mutations. In conclusion, the absence of vestibular and retinal symptom in the affected patients suggests that these families have the isolated non-syndromic hearing loss DFNB2 (nonsyndromic autosomal recessive hearing loss) presentation, instead of USH1B.

Distribution and features of hematological malignancies in Eastern Morocco: a retrospective multicenter study over 5 years.

BACKGROUND: Hematological malignancies (HM) are a public health problem. The pattern and distribution of diagnosed hematological cancers vary depending on age, sex, geography, and ethnicity suggesting the involvement of genetic and environmental factors for the development of these diseases. To our knowledge, there is no published report on HM in the case of Eastern Morocco. In this report we present for the first time the overall pattern of HM for this region. METHODS: Retrospective descriptive study of patients diagnosed with HM between January 2008 and December 2012 in three centres in Eastern Morocco providing cancer diagnosis, treatment or palliative care services. The FAB (French-American-British) classification system has been taken into account in the analysis of myeloid and lymphoid neoplasms. RESULTS: In this study, a total of 660 cases of HM were registered between January 2008 and December 2012. Overall, 6075 cases of cancers all sites combined were registered during this study period, indicating that HM account for around 10.9 % (660/6075) of all cancers recorded. Among the 660 registered cases of HM, 53 % were males and 47 % were females, with a male to female ratio of 1.1. Thus, overall, men are slightly more affected with HM than women. By contrast, a female predominance was observed in the case of Hodgkin's lymphoma (HL), myeloproliferative neoplasms (MPN), acute myeloid leukemia (AML) and the myelodysplastic syndrome (MDS). HM occur at a relatively young age, with an overall median age at diagnosis of 54 years. Non-Hodgkin's lymphoma (NHL) was the most common HM accounting for 29.7 % of all HM, followed by HL, MPN, multiple myelomas (MM), chronic lymphocytic leukemia (CLL), AML, MDS, acute lymphoblastic leukemia (ALL), and Waldenström macroglobulinemia (WM). The majority of HM cases have been observed among patients aged 60 years and over (40.4 % of HM). Among this age group, NHL was the most common HM. In adolescents, HL was the most frequent HM. CONCLUSIONS: This study provided for the first time the pattern and distribution of HM in Eastern Morocco. Our findings justify the need to establish a regional cancer registry as a first step in blood cancer control in Eastern Morocco.

Recessive TBC1D24 Mutations Are Frequent in Moroccan Non-Syndromic Hearing Loss Pedigrees.

Mutations in the TBC1D24 gene are responsible for four neurological presentations: infantile epileptic encephalopathy, infantile myoclonic epilepsy, DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation and seizures) and NSHL (non-syndromic hearing loss). For the latter, two recessive (DFNB86) and one dominant (DFNA65) mutations have so far been identified in consanguineous Pakistani and European/Chinese families, respectively. Here we report the results of a genetic study performed on a large Moroccan cohort of deaf patients that identified three families with compound heterozygote mutations in TBC1D24. Four novel mutations were identified, among which, one c.641G>A (p.Arg214His) was present in the three families, and has a frequency of 2% in control Moroccan population with normal hearing, suggesting that it acts as an hypomorphic variant leading to restricted deafness when combined with another recessive severe mutation. Altogether, our results show that mutations in TBC1D24 gene are a frequent cause (>2%) of NSHL in Morocco, and that due to its possible compound heterozygote recessive transmission, this gene should be further considered and screened in other deaf cohorts.

Association analysis of IGF2BP2, KCNJ11, and CDKAL1 polymorphisms with type 2 diabetes mellitus in a Moroccan population: a case-control study and meta-analysis.

Associations with type 2 diabetes mellitus have been identified for variants CDKAL1 rs7756992, KCNJ11 rs5219, and IGF2BP2 rs4402960 in different populations. In a case-control study of 250 unrelated Moroccan diabetic patients and 250 healthy controls, we used TaqMan allelic discrimination assays to genotype the three SNPs and meta-analysis to investigate the association between the polymorphisms and diabetes in Arab populations. The results showed a significant diabetes association only with the variant rs4402960 of the IGF2BP2 gene under additive 2 (GG vs. TT; p = 0.009) and recessive (TT vs. GG+GT; p = 0.003) models. Meta-analysis indicated significant association between the IGF2BP2 rs4402960 and CDKAL1 rs7756992 polymorphisms and increased risk of diabetes in Arab populations. According to our results, the case-control study and meta-analysis revealed a significant association between the IGF2BP2 rs4402960 variant and type 2 diabetes in Moroccan and Arab populations.

Genetic and molecular analysis of the CLDN14 gene in Moroccan family with non-syndromic hearing loss.

BACKGROUND: Hearing loss is the most prevalent human genetic sensorineural defect. Mutations in the CLDN14 gene, encoding the tight junction claudin 14 protein expressed in the inner ear, have been shown to cause non-syndromic recessive hearing loss DFNB29. AIM: We describe a Moroccan SF7 family with non-syndromic hearing loss. We performed linkage analysis in this family and sequencing to identify the mutation causing deafness. MATERIALS AND METHODS: Genetic linkage analysis, suggested the involvement of CLDN14 and KCNE1 gene in deafness in this family. Mutation screening was performed using direct sequencing of the CLDN14 and KCNE1 coding exon gene. RESULTS: Our results show the presence of c.11C>T mutation in the CLDN14 gene. Transmission analysis of this mutation in the family showed that the three affected individuals are homozygous, whereas parents and three healthy individuals are heterozygous. This mutation induces a substitution of threonine to methionine at position 4. CONCLUSION: These data show that CLDN14 gene can be i mplicated in the development of hearing loss in SF7 family; however, the pathogenicity of c.11C>T mutation remains to be determined.

Analysis of CLDN14 gene in deaf Moroccan patients with non-syndromic hearing loss.

Mutations in the CLDN14 gene, encoding the tight junction claudin 14 protein has been reported to date in an autosomal recessive form of isolated hearing loss DFNB29. In order to identify the contribution of CLDN14 to inherited deafness in Moroccan population, we performed a genetic analysis of this gene in 80 Moroccan familial cases. Our results show the presence of 7 mutations: 6 being conservative and one leading to a missense mutation (C11T) which was found at heterozygous and homozygous states, with a general frequency of 6.87%. The pathogenicity of the resulting T4M substitution is under discussion. Finally, our study suggests that CLDN14 gene can be implicated in the development of hearing loss in the Moroccan population.

Mutation rate at 17 Y-STR loci in "Father/Son" pairs from moroccan population.

Precise knowledge of mutation rate at Y-STRs loci is essential for a correct evaluation of typing results in forensic casework and specially kinship genetic studies. In this study, we have examined 252 confirmed and unrelated father/son sample pairs from Moroccan population using the 17 Y-STR markers DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385a, DYS385b, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, and Y-GATA-H4 of the AmpFlSTR Yfiler™ kit used in routine casework. We observed a total of 15 single repeat mutations between fathers and sons as mutational events. Nine mutations resulted in the gain of a repeat in the son and six resulted in a loss of a repeat. The average mutation rate in the studied sample is 3.5×10(-3) (95% CI 2-5.8×10(-3)). Furthermore, Y-STRs mutation occurrence seems to be 4 times more frequent than autosomal STRs mutation in this sample.

A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss.

A subset of nuclear-encoded RNAs has to be imported into mitochondria for the proper replication and transcription of the mitochondrial genome and, hence, for proper mitochondrial function. Polynucleotide phosphorylase (PNPase or PNPT1) is one of the very few components known to be involved in this poorly characterized process in mammals. At the organismal level, however, the effect of PNPase dysfunction and impaired mitochondrial RNA import are unknown. By positional cloning, we identified a homozygous PNPT1 missense mutation (c.1424A>G predicting the protein substitution p.Glu475Gly) of a highly conserved PNPase residue within the second RNase-PH domain in a family affected by autosomal-recessive nonsyndromic hearing impairment. In vitro analyses in bacteria, yeast, and mammalian cells showed that the identified mutation results in a hypofunctional protein leading to disturbed PNPase trimerization and impaired mitochondrial RNA import. Immunohistochemistry revealed strong PNPase staining in the murine cochlea, including the sensory hair cells and the auditory ganglion neurons. In summary, we show that a component of the mitochondrial RNA-import machinery is specifically required for auditory function.

The c.242G>A mutation in LRTOMT gene is responsible for a high prevalence of deafness in the Moroccan population.

Congenital hearing impairment (HI) affects one in 1,000 newborns and has a genetic cause in 50 % of the cases. Autosomal recessive non-syndromic hearing impairment is responsible for 70-80 % of all hereditary cases of HI. Recently, it has been demonstrated that, mutations of LRTOMT are associated with profound nonsyndromic hearing impairment at the DFNB63 locus. The objective of this study is to evaluate the carrier frequency of c.242G>A mutation in LRTOMT gene and define the contribution of this gene in the etiology of deafness in Moroccan population. We screened 105 unrelated Moroccan families with non-syndromic HI and 120 control individuals for mutation in the exon 8 of the LRTOMT gene, by sequencing and PCR-RFLP. The Homozygous c.242G>A mutation was found in 8.75 % of the families tested and in 4.16 % of control in the heterozygous state. Our results show that after the GJB2 gene mutation in LRTOMT gene is the second cause of congenital hearing impairment in Moroccan patients. This finding should facilitate diagnosis of congenital deafness of the affected subjects in Morocco.