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.

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.

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.

First report on molecular breast cancer subtypes and their clinico-pathological characteristics in Eastern Morocco: series of 2260 cases.

BACKGROUND: Breast cancer is the most frequent malignancy among women in Eastern Morocco. In this paper, we provide the first report on molecular breast cancer subtypes in this region. This is the largest population-based study on breast cancer among Moroccan women. METHODS: We analyzed 2260 breast cancer cases diagnosed at the Hassan II Regional Oncology Center between October 2005 and December 2012. Clinico-pathological and therapeutic features were studied. Molecular subtypes were determined and their associations with the clinico-pathological characteristics of the tumors were examined. RESULTS: The mean age at diagnosis was 48.7 years ±11.4. Invasive ductal carcinoma was the predominant histological type (77.1%), followed by lobular invasive carcinoma (15.3%). The mean size of breast tumors was 3.5 cm ± 1.96, and 84% of our patients are diagnosed with tumors of more than 2 cm. Histological grade II tumors were the most frequent (70.4%), followed by advanced histological grade (18%). Lymph node positive tumors were observed in 64.8% of cases and 29.3% of patients had distant metastasis. Most tumors were hormone receptor-positive (73%) and 28.6% were HER2 positive. 86.1% of patients with hormone receptor-positive breast cancer were given hormone therapy, while 68.9% of patients with HER2+ breast cancer received targeted therapy with Herceptin. Luminal A was the commonest molecular subtype, followed by Luminal B, Triple Negative and HER2. The highest prevalence of premenopausal patients was observed in Triple Negative subtype (72.2%), followed by HER2 (64.1%), Luminal B (62.2%), and Luminal A (55.1%). Luminal B subtype had a poorer prognosis than Luminal A. Compared with Triple Negative, HER2 subtype tend to spread more aggressively and is associated with poorer prognosis. CONCLUSIONS: Unlike Western countries, breast cancer occurs at an earlier age and is diagnosed at a more advanced stage in Eastern Morocco. In this region, hormone receptor-positive tumors are predominant and so the majority of breast cancer patients should benefit from hormone therapy. HER2 subtype presents an aggressive tendency, suggesting the importance of anti-HER2 therapy. This study will contribute in developing appropriate screening and cancer management strategies in Eastern Morocco.

Exploring Geographic Variability in Cancer Prevalence in Eastern Morocco: A Retrospective Study over Eight Years.

BACKGROUND: Malignant diseases have been believed to be more common in some areas of Eastern Morocco, but until now, cancer patterns have not been reported for this region. In this paper we present for the first time the cancer prevalence analysis in Eastern Morocco. METHODS: Cross-sectional study carried out among all patients diagnosed and/or treated with cancer at the Hassan II Regional Oncology Center (ROC) since it was established in October 2005 until December 2012. The ROC is the only hospital specialized in cancer care in Eastern Morocco. RESULTS: A total of 8,508 cases of cancer were registered among residents in Eastern Morocco, with a female to male ratio of 2.1. The mean age at diagnosis was 53.9 ± 15.2 years (median age = 53 years). Thus, unlike in Western countries, cancer in Eastern Morocco afflicts younger population. The areas of Eastern Morocco did not differ significantly by mean age at diagnosis (p = 0.061). However, these regions differed significantly by sex ratio (p < 0.001). The highest sex ratio was observed in Figuig, with a female to male ratio of 3.1 (75.4% of the registered case were females), followed respectively by Taourirt, Oujda-Angad, Berkane, Nador-Driouch and Jerada. Clear variation in the distribution of cancer types between areas of Eastern Morocco was observed, both in males and females (p < 0.001). Furthermore, the areas of Eastern Morocco differed significantly by cancer prevalence (p < 0.001). The highest age-standardized five-year prevalence proportion was observed in Oujda-Angad with 420.2 per 100,000, followed respectively by Berkane (311.4), Jerada (287.8), Taourirt (269.3), Nador-Driouch (213.6) and Figuig (194.4). Trends in the five-year prevalence proportions decreased in Oujda-Angad, Berkane and Jerada throughout the study period, while an increasing trend was observed in Nador-Driouch, Taourirt and Figuig. CONCLUSIONS: For the first time, our study presents the pattern and distribution of diagnosed cancers in Eastern Morocco. Our study illustrates substantial differences in cancer patterns between areas of Eastern Morocco. These findings are important for cancer control and highlight the need to develop program aiming at controlling and preventing the spread of major cancer sites in Eastern Morocco, particularly in areas with increased cancer prevalence rates.

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.