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.

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.

[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.