A case report of two Moroccan patients with hereditary neurological disorders and molecular modeling study on the S72L de novo PMP22 variant.

Hereditary neurological disorders represent a wild group of hereditary illnesses affecting mainly the nervous system, the majority of which have a Mendelian inheritance pattern. Here we present the case of two Moroccan patients each affected by a different hereditary neurological disorder. In the first patient WES analysis revealed the presence of the p.Ser72Leu de novo mutation in the PMP22 gene reported for the first time in Africa, specifically in Morocco. This variant is predicted to be in a mutation "hot-spot" region causing Dejerine-Sottas syndrome called also Charcot-Marie-Tooth type 3. The molecular modeling study suggests an important alteration of hydrogen and hydrophobic interactions between the residue in position 72 of the PMP22 protein and its surrounding amino acids. On the other hand, the p.Ala177Thr mutation on the RNASEH2B gene, responsible of Aicardi-Goutières syndrome 2, was carried in a homozygous state by the second patient descending from a consanguineous family. This mutation is common among the Moroccan population as well as in other North African countries. The present results contributed to a better follow-up of both cases allowing better symptom management with convenient treatments.

Genetic heterogeneity in GJB2, COL4A3, ATP6V1B1 and EDNRB variants detected among hearing impaired families in Morocco.

BACKGROUND: Deafness is the most prevalent human sensorineural defect. It may occur as a result of an external auditory canal involvement, or a deficiency in the sound conduction mechanism, or an impairment of the cochlea, the cochlear nerve or central auditory perception. The genetic causes are the most common, as approximately 70% of hearing disorders are of hereditary origin, divided into two groups, syndromic (associated with other symptoms) and no syndromic (isolated deafness). METHODS: A whole exome sequencing was performed to identify the genetic cause of hearing loss in six Moroccan families and Sanger sequencing was used to validate mutations in these genes. THE RESULTS: The results of four out of the six families revealed four genetic variants in the genes GJB2, COL4A3, ATP6V1B1 and EDNRB responsible for non-syndromic and syndromic hearing loss. Multiple Bioinformatics programs and molecular modelling predicted the pathogenic effect of these mutations. CONCLUSIONS: We identified in Moroccan deaf patients four homozygous mutations. These results show the importance of whole exome sequencing to identify pathogenic mutations in heterogeneous disorders with multiple genes responsible.

c.754T>A homozygous mutation described for the first time in three Moroccan patients with Gaucher disease.

Gaucher disease (GD) is a lysosomal storage disorder caused by glucocerebrosidase (GBA) deficiency. There are three subcategories of GD: Type 1 is characterized by the absence of primary central nervous system involvement; type 2 is an acute neuropathic disorder; and type 3 is chronic neuropathic. The correlation between genotype and phenotype is sometimes difficult to establish. The F213I (c.754T>A p.Phe252Ile) mutation was reported to be a unique mutation in Asia. To our knowledge, this is the first time the c.754T>A p.(Phe252Ile) mutation (homozygous state) is reported in a Moroccan population and is associated with GD type 2 (two patients) and GD type 3 (one patient).

Molecular diagnosis of Alpha-sarcoglycanopathies by NGS in seven Moroccan families and report of two novel variants.

BACKGROUND: Limb-girdle muscular dystrophies constitute a heterogeneous group of neuromuscular diseases, both clinically and genetically. Limb-girdle muscular dystrophy by alpha-sarcoglycan deficiency or LGMD R3 α-sarcoglycan-related is a subtype of the autosomal recessive sarcoglycanopathies caused by variants in the alpha-sarcoglycan gene (SGCA) at 17q21.33. It appears in childhood by progressive weakness of pelvic and/or scapular girdle muscles and calf hypertrophy, with a wide range of clinical inter- and intra-familial clinical variability. AIMS: Our report extends the molecular spectrum of SGCA gene with the identification of variant disease causing and will help for better management of patients and genetic counseling of families. METHODS: In our study, seven unrelated families presented a clinical and paraclinical picture consistent with alpha-sarcoglycanopathy. A molecular study using Next-Generation Sequencing (NGS) was carried out on them. RESULTS: Six different homozygous variants of the SGCA gene were identified in the patients analyzed, including four previously reported variants and two novel variants predicted to be deleterious by the prediction tools. CONCLUSIONS: Our results expand the spectrum of variants in Moroccan patients with sarcoglycanopathy, specifically LGMDR3, most importantly as this form is not common in the Moroccan population.

Virological characterization of Hepatitis B virus infection in Morocco: A ten-years study (2014 - 2023).

In alignment with Morocco's national strategy for eliminating viral hepatitis, we aimed to characterize and update the virological profile of chronic hepatitis B patients. Demographic, serological and molecular parameters of 804 HBsAg-positive patients were retrospectively analyzed. Overall, 58.24 % were HBV-positive (55.37 % males, p = 0.74). The median age was 46 years (37-57). Patients ≤ 24 years comprised 5 % of HBsAg-positive and 4.34 % of HBV-positive cases. The median viral load was 2.62 log10 IU/mL (1.87-3.44). The prevalent genotypes were D (91.04 %), A (7.55 %) and E (1.41 %). Liver enzymes were normal in most of cases. 91.04 % of patients were HBeAg-negative, with 92.23 % having genotype D (p < 0.001). Co-infection rates with other hepatitis viruses were low. Significant associations were found between HBeAg-negative status, genotype D, viral load, and liver enzyme levels (p < 0.001). We highlighted the need for prenatal HBsAg screening for pregnant women and prioritizing the birth-dose vaccine to prevent mother-to-child transmission, especially after the COVID-19 pandemic.

Effect of COVID-19 lockdown on Moroccan patients with type 1 and type 2 diabetes.

Background: The implementation of coronavirus disease of 2019 (COVID-19) lockdown has affected the daily practices of subjects with chronic diseases such as diabetes and caused negative impact on their lifestyle and habits such as physical activity, dietary habits and accessibility to medications. Diabetic people are considered the most vulnerable groups to COVID-19, and the lockdown measure has disturbed the diabetes self-management. In our study, we aimed to assess, for the first time at the regional level (Souss Massa Region), the COVID-19 lockdown impact on HbA1c levels in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D). We carried out a cross-sectional quantitative analysis at the health center of the industrial district in Agadir City. Results: We found a significant improvement in post-lockdown mean ± SD HbA1c in 150 subjects suffering from T1D and T2D; p = 0.005). Our analysis revealed a significant association of HbA1c deviation with educational level and medical coverage (p = 0.01). No significant association was detected between HbA1c deviation and age, gender, weight, height, current BMI status, fasting blood sugar, family history, urban or rural areas, marital status, professional activity, socioeconomic income, type of diabetes, dietary, comorbidities, diabetic complications, housing, adherence to the dietary recommendations, physical activity, medical appointments, stopping medication, self-monitoring, fasting and anxiety about getting COVID-19. Conclusions: COVID-19 lockdown had no deleterious effect on HbA1c levels in Moroccan patients with T1D and T2D.

AKT1 and PIK3CA activating mutations in Moroccan bladder cancer patients´ biopsies and matched urine.

Introduction: in cancer cells, activating mutations in PIK3CA and AKT1 genes, major players of PI3K-AKT-mTOR signalling pathway, are widely reported in many cancers and present attractive targets for the identification of new therapeutics and better cancer management. The present study was planned to evaluate the mutational status of PIK3CA and AKT1 genes in bladder cancer patients and to assess the association between these mutations and patients´ clinico-pathological features. Methods: in this prospective study, bladder cancer biopsies and matched urine sediments samples were collected form 70 patients. Mutations were assessed by deoxyribonucleic acid (DNA) sequencing and correlation with clinico-pathological data was performed using SPSS software. Results: AKT1 alterations were poorly detected. Only one patient with pT1 stage and high-grade tumour carried the E17K mutation. In PIK3CA exon 9, 2 point mutations, E545K and Q546E, and a SNP (E547E) were reported, whereas in exon 20, 2 point mutations (L989V and H1047R) and 2 SNPs (I1022I and T1025T) were detected. PIK3CA mutations were mainly observed in early stages and high-grade tumours. Statistical analysis showed no significant association between the studied AKT1 and PIK3CA mutations and patients´ clinico-pathological parameters (p > 0.05). Detection of these mutations in voided urine samples showed a high specificity (100%) for both genes and a moderate sensitivity: 100% for AKT1 and 66.7% for PIK3CA genes. Conclusion: this study shows clearly that mutations in AKT1 and PIK3CA are rare events and could not be considered as valuable biomarkers for bladder cancer management.

Prevalence of liver fibrosis and cirrhosis in 699 Moroccan patients with chronic hepatitis C.

INTRODUCTION: chronic hepatitis C (CHC) can cause severe complications, including fibrosis and cirrhosis. Very little is known about the prevalence of these complications in the Moroccan population. METHODS: the prevalence of liver fibrosis and cirrhosis using a non-invasive blood test (FibroTest and ActiTest) was studied in 699 Moroccan patients with CHC for 4 years (from January 2014 to December 2017). The serum immunological markers: α2-macroglobulin, haptoglobin, apolipoprotein A1 were analyzed nephelometrically on BN ProSpec® System. The serum biochemical markers: γ-glutamyltransferase, alanine aminotransferase, and bilirubin were performed using the VITROS® Chemistry System Ortho Clinical Diagnostic. A 699 patients with CHC were identified. RESULTS: the overall prevalence of cirrhosis (F4) was estimated at 31.8%. Thirteen point nine percent (13.9%) of patients with cirrhosis had a risk of developing esophageal varices and a 3.3% risk of developing primary liver cancer. The association between cirrhosis and age showed an increase in prevalence after age 55 years old [OR=7.68(95%CI=4.9-12.2); p<0.0001]. No significant association for cirrhosis was found for sex. CONCLUSION: according to the results of FibroTest, 32% of patients with CHC had cirrhosis. The older age was independently associated with liver cirrhosis.

Microsatellite Instability Analysis in Gastric Carcinomas of Moroccan Patients.

Aim: To investigate correlations between microsatellite instability (MSI) and the phenotype, clinicopathological features, and overall survival (OS) in Moroccan gastric cancer (GC) patients. We evaluated the mutation frequency of 22 MSI-target genes in MSI-positive tumors. Materials and Methods: MSI evaluation were performed for 97 gastric tumors by multiplex polymerase chain reaction (PCR) using a panel of five quasimonomorphic mononucleotide repeat markers (NR27, NR21, NR24, BAT25, and BAT26). The mutation profiles of 22 MSI-target genes were assessed by multiplex PCR and genotyping. Kaplan-Meier curves, the log-rank test, and the Cox proportional hazard regression model were used to conduct survival analyses. Results: Microsatellite stable (MSS) status was observed in 77/97 (79.4%) gastric cancer samples, MSI-Low in 7 (7.2%) samples, and MSI-High (MSI-H) in 13 (13.4%) cases. The MSI-H phenotype was significantly associated with older age (p = 0.004), tumor location (p < 0.001), and intestinal-type of Lauren classification (p < 0.001). Among the 22 MSI target genes analyzed, the most frequently altered genes were HSP110 (84.6%), EGFR (30.8%), BRCA2 (23.1%), MRE11 (23.1%), and MSH3 (23.1%). Multivariate analysis revealed the MSS phenotype (Hazard ratio, 0.23; 95% confidence interval, 0.7-7.4; p = 0.014) as an independent indicator of poor prognosis in our population. Conclusions: This study is the first analysis of MSI in Moroccan GC patients. MSI-H GCs have distinct clinicopathological features and an improved OS. We have identified candidate target genes altered in MSI-positive tumors with potential clinical implications. These findings can guide immunotherapy designed for Moroccan GC patients.

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.

Study of Clinical and Biological Characteristics of Moroccan Covid-19 Patients With and Without Olfactory and/or Gustatory Dysfunction.

BACKGROUND: The epidemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), presents a significant and urgent threat to global health. This alarming viral infection, declared as pandemic by the WHO in February 2020, has resulted millions of infected patients and thousands of deaths around the world. In Morocco, despite the efforts made by the authorities, the SARS-CoV-2 continues to spread and constitutes a burden of morbidity and mortality. The objective of this study is to describe clinical characteristics of COVID-19 Moroccan patients and to establish the relationship between specific clinical symptoms, namely ageusia and/or anosmia, with these characteristics. METHODS: We performed a descriptive, non-interventional cross-sectional study analyzing data from 108 patients admitted to the VINCI clinic, Casablanca (Morocco). The database includes 39 parameters including epidemiological characteristics, anthropometric measurements and biological analyzes. RESULTS: The average of age of the patients was 43.80 ± 15.75 years with a sex ratio of 1:1. The mean body mass index of the patients was 25.54 ± 4.63 Kg/m2. The majority of patients had, at least, one comorbidity and among 75% symptomatic patients, about 50% had, at least, three symptoms namely, fever (40.7%), cough (39.8%), myalgia (28.7%), and anosmia and/or ageusia (20.4%). From biological analyzes, we noticed lymphopenia and an elevated protein C reactive and lactate dehydrogenases levels in 24.1, 36.1, and 35.2% of patients, respectively. A disturbance in liver function markers was observed in 15.7% of cases. For the other hemostasis parameters, high levels of prothrombin and platelets were reported in 14.6 and 14.8% of patients, respectively. Comparisons related to the presence of anosmia and/or ageusia did not show any difference for demographic and anthropometric characteristics, while a possibility of a significant difference was revealed for certain biological parameters, particularly the levels of lymphocytes, D-dimer and troponin. CONCLUSION: This study provides significant findings that will be used not only to supplement previous studies carried out in Morocco in order to resume the epidemiological situation in comparison with other countries, but also to improve the quality of the diagnosis of COVID-19 patients by identifying all the symptoms of the disease and better understanding its clinical outcomes.

Comparison of Non-radiographic Axial Spondyloarthritis and Ankylosing Spondyltis from a Single Rheumatology Hospital in Morocco.

BACKGROUND: According to the new classification criteria developed by The Assessment of SpondyloArthritis International Society, patients with axial spondyloarthritis (axSpA) can be classified in 2 subgroups: Patients with radiographic axial spondyloarthritis: ankylosing spondylitis patients (AS) and those with non-radiographic axial spondyloarthritis (nr-axSpA). OBJECTIVE: The aim of the present study is to describe and discuss the differences and similarities between the two subgroups. PATIENTS AND METHODS: A cross-sectional study was conducted in a single rheumatology hospital in Morocco. These included patients diagnosed as having axial spondyloarthritis according to ASAS criteria 2010, during a period of 6 years. The AS and the nr-axSpA subgroups were compared for the various axSpA-related variables. RESULTS: Of the 277 patients with a diagnosis of axial SpA who were included in this study, 160 had AS and 117 had nr-axSpA. AS and nr-ax-SpA shared a similar age at diagnosis, similar prevalence of low back pain, lumbar stiffness, extra-articular manifestations, BASDAI and BASFI. In the multivariate analysis, AS patients were mainly male with cervical stiffness, enthesitis, coxitis and high level of ESR (erythrocyte sedimentation rate). The females generally had a family history of SpA and arthritis and were associated to the nr-axSpA form in the univariate analysis. CONCLUSION: This was the first study to characterise patients with AS and nr-axSpA in Morocco. Consistent with other studies published, this study showed that patients with nr-axSpA and patients with AS shared a comparable degree of disease burden.

The First Molecular Screening of MLH1 and MSH2 Genes in Moroccan Colorectal Cancer Patients Shows a Relatively High Mutational Prevalence.

INTRODUCTION: Lynch syndrome (LS) is an autosomal dominant disorder characterized by early age of onset and increased risk of developing extracolonic tumors. Molecular diagnosis of LS requires identification of germline mutations in one of the Mismatch Repair (MMR) genes. AIM: The objective of the study was to investigate the prevalence of MLH1/MSH2 mutation carriers among Moroccan patients with colorectal cancer (CRC) in a hospital-based cohort. METHODS: In this study, 214 CRC patients from COLORECFez cohort were included. Patients whose tumors showed MMR deficiency (MMR-D) and wild-type BRAF were selected to undergo mutational analysis of the MLH1 and MSH2 genes using Sanger sequencing. RESULTS: A total of 24 MMR-D tumors were identified (11.2%) among 214 CRC tested for MMR protein expression. The BRAF p.Val600Glu mutation was absent in all tumors deficient for MLH1 protein. Molecular screening showed germline MMR mutations (MLH1/MSH2) in four cases, two of which fulfilled Amsterdam criteria II and two met at least one of the revised Bethesda guidelines. The estimated frequency of MLH1/MSH2 mutations in Moroccan CRC patients was 1.87%. CONCLUSIONS: The present study reports a relatively high incidence of MLH1/MSH2 (1.87%). These results confirm the contribution of MMR genes to CRC susceptibility in our population and provide evidence regarding the requirement of implementing a national screening program for LS in Morocco.

Non-Motor Symptoms of Parkinson's Disease and Their Impact on Quality of Life in a Cohort of Moroccan Patients.

BACKGROUND: Non-motor symptoms (NMSs) are a real burden in Parkinson's disease (PD). They may appear in early pre-symptomatic stage as well as throughout the disease course. However, their relationship with the deterioration of the patient's quality of life (QoL) is still under debate. This study aimed to investigate the prevalence of NMSs and their impact on the QoL in a cohort of Moroccan patients. METHODS: We carried out a cross-transactional study, where a total of 117 patients were submitted to a structured clinical interview and examination investigating motor and NMSs based on common and conventional scales. Motor symptoms were assessed by the UPDRS I-VI during ON condition. The NMSs were evaluated with common scales and their relationship with the QoL was investigated. RESULTS: The mean patient's age was 60.77 ± 11.36 years old, and the median disease duration was 6 years [2.5-9.5]. Motor's phenotype subtypes were the mixed form in 40.2% of patients, akinetic-rigid in 20.5% and a tremor-dominant form in 39.3%. The median Hoehn and Yahr staging was 2 [1-2.5]. Regarding NMSs, the most common were urinary dysfunctions (82.6%), sleep (80.6%), and gastrointestinal (80%) disorders. Other autonomic dysfunctions were also frequent: thermoregulatory dysfunctions 58.6%, cardiovascular troubles 50.9%, and sexual dysfunctions 47.9%. Depression was present in 47.9% and fatigue symptoms in 23.1%. The median score of SCOPA-AUT was 14 [7.75-21.80]. The median PD questionnaire 39-score index (PDQ39-SI) was 23.22% and the most affected dimension was "mobility." Univariate and multivariate analyses showed that the SCOPA-AUT score impacted the QoL (p = 0.001), especially the gastrointestinal (p = 0.007), and cardiovascular (p = 0.049) dimensions. CONCLUSION: Our data show that all patients have presented at least one NMS. Autonomic and sleep disorders were the most frequent, and in contrast to other studies, digestive and cardiovascular disorders were rather the factors influencing negatively the QoL of patients. Understanding the pathophysiology of these NMSs should be placed at the forefront in order to develop new therapeutic approaches by improving the QoL of PD patients.

Mutation Analysis of Consanguineous Moroccan Patients with Parkinson's Disease Combining Microarray and Gene Panel.

During the last two decades, 15 different genes have been reported to be responsible for the monogenic form of Parkinson's disease (PD), representing a worldwide frequency of 5-10%. Among them, 10 genes have been associated with autosomal recessive PD, with PRKN and PINK1 being the most frequent. In a cohort of 145 unrelated Moroccan PD patients enrolled since 2013, 19 patients were born from a consanguineous marriage, of which 15 were isolated cases and 4 familial. One patient was homozygous for the common LRRK2 G2019S mutation and the 18 others who did not carry this mutation were screened for exon rearrangements in the PRKN gene using Affymetrix Cytoscan HD microarray. Two patients were determined homozygous for PRKN exon-deletions, while another patient presented with compound heterozygous inheritance (3/18, 17%). Two other patients showed a region of homozygosity covering the 1p36.12 locus and were sequenced for the candidate PINK1 gene, which revealed two homozygous point mutations: the known Q456X mutation in exon 7 and a novel L539F variation in exon 8. The 13 remaining patients were subjected to next-generation sequencing (NGS) that targeted a panel of 22 PD-causing genes and overlapping phenotypes. NGS data showed that two unrelated consanguineous patients with juvenile-onset PD (12 and 13 years) carried the same homozygous stop mutation W258X in the ATP13A2 gene, possibly resulting from a founder effect; and one patient with late onset (76 years) carried a novel heterozygous frameshift mutation in SYNJ1. Clinical analysis showed that patients with the ATP13A2 mutation developed juvenile-onset PD with a severe phenotype, whereas patients having either PRKN or PINK1 mutations displayed early-onset PD with a relatively mild phenotype. By identifying pathogenic mutations in 45% (8/18) of our consanguineous Moroccan PD series, we demonstrate that the combination of chromosomal microarray analysis and NGS is a powerful approach to pinpoint the genetic bases of autosomal recessive PD, particularly in countries with a high rate of consanguinity.

Impact of I/D polymorphism of angiotensin-converting enzyme (ACE) gene on myocardial infarction susceptibility among young Moroccan patients.

OBJECTIVE: Our case-control study aimed to access the potential association of insertion/deletion (I/D) ACE (angiotensin converting enzyme) gene polymorphism with myocardial infarction (MI) risk of occurrence among a sample of Moroccan patients, especially young ones. RESULTS: Distribution of I/D ACE gene variant among cases vs controls, showed that healthy controls carried out higher frequency of wild type allele I compared to cases (23.5% vs 21.79% respectively), when cases were carrying higher frequency of mutant allele D (78.21% vs 76.5% for controls). Patients were-after this- divided into two groups of < 45 and > 55 years of age, to investigate whether or not younger patients carried out higher frequency of the mutant allele D, than older ones. As expected, < 45 years old patients carried out more DD genotype than older ones (68.9% vs 54.6% respectively), and higher frequency of mutant allele D (81.08% vs 75% respectively). Besides, a tendency to a positive association was found under the recessive genetic transmission model (OR [95% CI] = 1.85 [0.93-3.69], P = 0.08), suggesting that the I/D ACE polymorphism may be associated with MI occurrence among younger patients (< 45 years of age).

Polymorphisms in oxidative pathway related genes and susceptibility to inflammatory bowel disease.

AIM: To investigate whether common variants in the oxidative pathway genes influence inflammatory bowel disease (IBD) risk among Moroccan patients. METHODS: The distribution of (TAAA)n_rs12720460 and (CCTTT)n _rs3833912 NOS2A microsatellite repeats, HIF-1A_rs11549467 and NFKB1-94ins/delATTG_rs28362491 was analyzed in 507 subjects grouped in 199 IBD and 308 healthy controls. Genotyping was performed with polymerase chain reaction-fluorescent method and the TaqMan® allelic discrimination technology. RESULTS: The allele and genotype frequencies of HIF1A_ rs11549467, NFKB1_rs28362491 and NOS2A_ (TAAA)n did not differ significantly between patients and controls. Analysis of NOS2A_ (CCTTT)n markers evidenced differences between patients and healthy controls. A preferential presence of the (CCTTT)8 (P = 0.02; OR = 1.71, 95%CI: 1.07-2.74), (CCTTT)14 (P = 0.02; OR = 1.71, 95%CI: 1.06-2.76) alleles in IBD, (CCTTT)8 (P = 0.008; OR = 1.95, 95%CI: 1.17-3.23) in CD and (CCTTT)7 (P = 0.009; OR = 7.61, 95%CI: 1.25-46.08), (CCTTT)11 (P = 0.05; OR = 0.51, 95%CI: 0.25-1.01), (CCTTT)14 (P = 0.02; OR = 2.05, 95%CI: 1.07-3.94), (CCTTT)15 (P = 0.01; OR = 2.25, 95%CI: 1.16-4.35) repeats in UC patients indicated its possible association with higher disease risk which need to be confirmed in a larger sample size. CONCLUSION: Our results suggest that the NOS2A_ (CCTTT)n gene variations may influence IBD susceptibility in the Moroccan population.

Novel presenilin mutations within Moroccan patients with Early-Onset Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive brain disorder that causes gradual and irreversible loss of higher brain functions and is the most common cause of dementia in the elderly, as assessed by autopsy and clinical series. Furthermore, it has an annual incidence of approximately 3% in the 65-74-year-old age group. This incidence rate doubles with every increment of 5 years above the age of 65. In Morocco, AD affects almost 30,000 individuals and this number will possibly increase to 75,000 by 2020 (projections of the World Health Organization (WHO)). Genetically, AD is caused by a mutation in one of at least 3 genes: presenilin 1 (PS1), presenilin 2 (PS2) and the amyloid precursor protein (APP). Most cases are late onset and apparently sporadic, most likely as a result of a combination of environmental and non-dominant genetic factors. In Morocco, the genes predisposing individuals to AD and predicting disease incidence remain elusive. The purpose of the present study was to evaluate the genetic contribution of mutations in PS1 and PS2 genes to familial early-onset AD cases and sporadic late-onset AD cases. Seventeen sporadic late-onset AD cases and eight familial early-onset AD cases were seen at the memory clinic of the University of Casablanca Neurology Department. These patients underwent standard somatic neurological examination, cognitive function assessment, brain imaging and laboratory tests. Direct sequencing of each exon in PS1 and PS2 genes was performed on genomic DNA of AD patients. Further, we identified 1 novel frameshift mutation in the PS1 gene and 2 novel frameshift mutations in the PS2 gene. Our mutational analysis reports a correlation between clinical symptoms and genetic factors in our cases of Early-Onset Alzheimer's Disease (EOAD). These putative mutations cosegregate with affected family members suggesting a direct mutagenic effect.