Novel mutation in the TGFBI gene in a Moroccan family with atypical corneal dystrophy: a case report.

BACKGROUND: Corneal dystrophies (CDs) are a heterogeneous group of bilateral, genetically determined, noninflammatory bilateral corneal diseases that are usually limited to the cornea. CD is characterized by a large variability in the age of onset, evolution and visual impact and the accumulation of insoluble deposits at different depths in the cornea. Clinical symptoms revealed bilateral multiple superficial, epithelial, and stromal anterior granular opacities in different stages of severity among three patients of this family. A total of 99 genes are involved in CDs. The aim of this study was to identify pathogenic variants causing atypical corneal dystrophy in a large Moroccan family and to describe the clinical phenotype with severely different stages of evolution. CASE PRESENTATION: In this study, we report a large Moroccan family with CD. Whole-exome sequencing (WES) was performed in the three affected members who shared a phenotype of corneal dystrophy in different stages of severity. Variant validation and familial segregation were performed by Sanger sequencing in affected sisters and mothers and in two unaffected brothers. Whole-exome sequencing showed a novel heterozygous mutation (c.1772C > A; p.Ser591Tyr) in the TGFBI gene. Clinical examinations demonstrated bilaterally multiple superficial, epithelial and stromal anterior granular opacities in different stages of severity among three patients in this family. CONCLUSIONS: This report describes a novel mutation in the TGFBI gene found in three family members affected by different phenotypic aspects. This mutation is associated with Thiel-Behnke corneal dystrophy; therefore, it could be considered a novel phenotype genotype correlation, which will help in genetic counselling for this family.

Medicines Acceptability in Hospitalized Children: An Ongoing Need for Age-Appropriate Formulations.

Although knowledge on medicine acceptability remains fragmented, this multi-faceted concept has emerged as a key factor for compliance in pediatrics. In order to investigate the acceptability of medicines used in the University Medical Centre Ibn Sina (CHIS) of Rabat, Morocco, an observational study was conducted. Using a multivariate approach integrating the many aspects of acceptability, standardized observer reports were collected for 570 medicine intakes in patients up to the age of 16, then analyzed on a reference framework. Tablets appeared to be well accepted in children greater than 6 years old, but were crushed/dissolved for 90% of the 40 children aged from 3 to 5, and 100% of the 38 patients younger than 3. Moreover, the prescribed dose was fully taken for only 52% and 16% of these younger children, respectively. Despite this, tablets represented 24% of evaluations in children from 3 to 5 and 20% in infants and toddlers. Oral liquid preparations appeared to be better accepted than tablets in preschoolers, but not for those under 3. Overall, these findings highlight the lack of suitable alternatives for the younger children, especially for formulations of antiepileptics, antithrombotic, and psycholeptic agents in the local context.

Elimination of trachoma from Morocco: a historical review.

Since the 1950s, the Kingdom of Morocco has been and remains one of the pioneers in the fight against trachoma, a disease that has completely disappeared in the majority of its national territory, but some endemic pockets have persisted and pose a health risk, particularly for children and women. Morocco finds itself today, thanks to years of joint efforts, at the forefront of the world stage of the fight against trachoma. The country has demonstrated through its experience the effectiveness and relevance of the "SAFE" strategy - an extensive programme designed to tackle trachoma and its complications. The strategy is complex in its implementation and requires the synergy of a set of actors dedicated to specific activities, whether medico-surgical management activities aimed at setting up a physical project for local development, or information and awareness-raising activities. The key to the long-term success of eliminating blinding trachoma was not only to link distribution of drugs to the entire project area for several years to reduce substantially the reservoir of human- to-human transmission, but also to ensure permanence. In addition, services that provide quality palpebral surgery and especially repeat treatment campaigns with antibiotics, as well as health education campaigns and the promotion of personal and collective hygiene have generated sustainable changes in the living environment of receiving populations.

Homozygous frameshift mutations in FAT1 cause a syndrome characterized by colobomatous-microphthalmia, ptosis, nephropathy and syndactyly.

A failure in optic fissure fusion during development can lead to blinding malformations of the eye. Here, we report a syndrome characterized by facial dysmorphism, colobomatous microphthalmia, ptosis and syndactyly with or without nephropathy, associated with homozygous frameshift mutations in FAT1. We show that Fat1 knockout mice and zebrafish embryos homozygous for truncating fat1a mutations exhibit completely penetrant coloboma, recapitulating the most consistent developmental defect observed in affected individuals. In human retinal pigment epithelium (RPE) cells, the primary site for the fusion of optic fissure margins, FAT1 is localized at earliest cell-cell junctions, consistent with a role in facilitating optic fissure fusion during vertebrate eye development. Our findings establish FAT1 as a gene with pleiotropic effects in human, in that frameshift mutations cause a severe multi-system disorder whereas recessive missense mutations had been previously associated with isolated glomerulotubular nephropathy.

Global initiative for congenital toxoplasmosis: an observational and international comparative clinical analysis.

Globally, congenital toxoplasmosis remains a significant cause of morbidity and mortality, and outbreaks of infection with T. gondii represent a significant, emerging public health burden, especially in the developing world. This parasite is a threat to public health. Disease often is not recognized and is inadequately managed. Herein, we analyze the status of congenital toxoplasmosis in Morocco, Colombia, the United States, and France. We identify the unique challenges faced by each nation in the implementation of optimal approaches to congenital toxoplasmosis as a public health problem. We suggest that developed and developing countries use a multipronged approach, modeling their public health management protocols after those in France. We conclude that education, screening, appropriate treatment, and the development of novel modalities will be required to intervene successfully in caring for individuals with this infection. Gestational screening has been demonstrated to be cost-effective, morbidity-sparing, and life-saving. Recognition of the value and promise of public health interventions to prevent human suffering from this emerging infection will facilitate better patient and societal outcomes.

[Post-traumatic scleromalacia]. / Scléromalacie post traumatique.

We here report the case of a 18-year old patient who was referred for evaluation of pigmented subconjunctival tumor of the left eye mimicking uveal melanoma. The patient reported that the lesion had evolved rapidly during the previous months. Eye exam showed prominent dark brown lesion adjacent to the limbus between 3 and 9 hours, measuring 10 mm x 6 mm (A). Ultrasonographic biomicroscopy revealed cystic structure communicating with the vitreous cavity, suggesting the diagnosis of uveal hernia rather of melanoma. During a more thorough interview, the patient reported that he had undergone transfixing keratoplasty for cloudy patch secondary to blunt trauma from stone's throw dating back 10 years. We assumed that the scleral wall had been damaged, leading to the development of scleromalacia with uveal hernia. The patient had recently had an acute episode of vomiting which could have lead to an increase in lesion size. The patient was followed up for several weeks, during which the lesion was stable. The patient underwent surgery with successful uveal tissue reintegration and sclera closure (B).

Severe early onset retinitis pigmentosa in a Moroccan patient with Heimler syndrome due to novel homozygous mutation of PEX1 gene.

Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. It is the mildest form known to date of peroxisome biogenesis disorder caused by hypomorphic mutations of PEX1 and PEX6 genes. We report on a second Moroccan family with Heimler syndrome with early onset, severe visual impairment and important phenotypic overlap with Usher syndrome. The patient carried a novel homozygous missense variant c.3140T > C (p.Leu1047Pro) of PEX1 gene. As standard biochemical screening of blood for evidence of a peroxisomal disorder did not provide a diagnosis in the individuals with HS, patients with SNHL and retinal pigmentation should have mutation analysis of PEX1 and PEX6 genes.

Genotype-phenotype correlation in Moroccan patients with primary congenital glaucoma.

PURPOSE: To investigate the genotype-phenotype correlation in a large cohort of Moroccan primary congenital glaucoma (PCG) in which CYP1B1 mutation spectrum was recently reported by our group. METHODS: This study included 94 patients from 84 unrelated Moroccan PCG families with or without CYP1B1 mutations. Clinical features, severity of the phenotype, and prognosis were mainly compared in patients with no CYP1B1 mutations, double CYP1B1 null alleles or nondouble null but other CYP1B1 mutations; most of them were hypomorphic mutations. Statistical analyses were performed using SAS and SPSS softwares. Significance was set at P<0.05. RESULTS: Mean of intraocular pressure, corneal diameter and number of surgery values and cup-to-disc ratios, and percentages of patients with bilateral PCG, eyes with severe opacities and severe phenotype, and those that needed >1 trabeculectomy were significantly higher in the CYP1B1 mutation carriers (n=51) than in the no CYP1B1 mutation group (n=43). The same results were observed when patients with double CYP1B1 null alleles (n=34) were compared with those with no CYP1B1 mutation. The comparison between the no CYP1B1 mutation patients and those with nondouble null but other CYP1B1 mutations (n=17) showed significant differences in the percentage of bilateral PCG and percentages of eyes with severe opacities and severe phenotype. When the double CYP1B1 null allele carriers were compared with the nondouble null but other CYP1B1 mutation group, only significant differences were observed in the mean number of surgery values. Multivariate analysis revealed that, after adjustment of the parameters that showed significant differences in univariate analyses, corneal diameter was the main factor explaining the severity of PCG only in the double CYP1B1 null allele carriers. CONCLUSIONS: This is the first report of genotype-phenotype correlation in a large cohort of Moroccan PCG. Our results revealed that the worst phenotype and prognosis were observed in the double null CYP1B1 allele carriers followed by the nondouble null but other CYP1B1 mutations. This will contribute to the prediction of the prognosis of the disease.

[Phytoplankton distribution in the upwelling areas of the Moroccan Atlantic coast localized between 32°30'N and 24°N]. / Distribution du phytoplancton dans les zones d'upwelling de la côte atlantique marocaine située entre les latitudes 32°30'N et 24°N.

Marine phytoplankton was studied in January and July 2002 along of four transects: 32°30'N, 29°N, 24°30'N and 24°N. A total of 142 taxa were recorded in this area. The maximal specific richness, both in summer and in winter, was registered around Dakhla (24°N). The global spatiotemporal variability of species richness and specific diversity showed that the most structured and species-rich populations are situated in the coastal areas. The vertical variation of the two parameters showed homogeneity between depth levels. The maximal phytoplanktonic densities are recorded in the southern transects due to the permanent upwelling activity in the southern Atlantic coast. The bathymetric distribution of densities was more heterogeneous during summer, characterized by a high intensity of upwelling. The species Thalassionema nitzschioides, Asterionellopsis glacialis, Melosira, Chaetoceros and Leptocylindrus minimus are indicators of upwelling.

[Copepods distribution in relation to a Cape Ghir upwelling filament (Moroccan Atlantic coast)]. / Distribution des copépodes en relation avec la dynamique du filament de Cap Ghir, (Côte atlantique du Maroc).

The study of the Cape Ghir upwelling filament (31°N) focalizes to describe the dispersive mechanism, caused by the upwelling. The zooplankton was sampled during five oceanographic cruises conducted between 2008 and 2009. Surface temperature and chlorophyll "a" were also measured along with sampling. The distribution of environmental parameters accused extensions that show the path of the filament. Copepods constitute the largest fraction of zooplankton community and represented by 86 species, majorly dominated by Acartia clausi and Oncaea venusta. A number of species of deep or cold waters have been recorded in the area corresponding to a net resurgence of cold water. The analysis of the copepods distribution allowed to view the path of the filament at different times of the year. The distribution of the species A. clausi, neritic specie was observed in the open ocean, shows a result of this dynamic.

Screening of CYP1B1 and MYOC in Moroccan families with primary congenital glaucoma: three novel mutations in CYP1B1.

PURPOSE: To investigate the contribution of cytochrome P4501B1 (CYP1B1) and myocillin (MYOC) mutations to primary congenital glaucoma (PCG) in Moroccan families. METHODS: This study included 90 unrelated families with PCG and 100 normal control individuals. Two previously reported CYP1B1 mutations (g.4339delG and p.G61E) were first screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The coding exons of CYP1B1 were sequenced in g.4339delG- and p.G61E-negative or heterozygous probands. Then the coding exons of MYOC were sequenced in patients who had no mutation in CYP1B1 or carried heterozygous CYP1B1 mutation. RESULTS: Twelve CYP1B1 mutations were identified in 43 PCG pedigrees. Three of them were novel (p.R163C, p.C470Y, and g.4330-4331delTG) and associated with moderate to severe phenotypes. Two novel intronic polymorphisms in CYP1B1 were identified in addition to those previously described. The g.4339delG was the most frequent mutation detected in 31 families (34.44%), followed by the p.G61E in seven families (7.77%). The remaining mutations (p.R163C, p.E173K, g.4330-4331delTG, p.E229K, p.R390S, p.R368H, p.R469W, p.C470Y, and g.7901-7913del13bp) were infrequent. One family with the p.R390S mutation showed both PCG and primary open angle glaucoma (POAG) phenotypes. One proband was heterozygous for p.T193K mutation in MYOC. This mutation has been initially associated with POAG, but never with PCG. CONCLUSIONS: Our results support that mutations in CYP1B1 are a major cause for PCG in the Moroccan population with a predominance of the g.4339delG mutation. Furthermore, these results demonstrate the diversity of CYP1B1 mutations, while suggesting a modest role of MYOC in Moroccan PCG.

Congenital rubella syndrome burden in Morocco: a rapid retrospective assessment.

BACKGROUND: WHO recommends that countries considering introduction of rubella vaccine into their immunisation programme assess their burden of congenital rubella syndrome, to determine whether vaccination is warranted. However, few guidelines exist for such assessments in developing countries. We retrospectively estimated the burden of congenital rubella syndrome in Morocco, and assessed our methods of rapid case finding. METHODS: We undertook case finding in the two cities with Morocco's main tertiary care referral centres, using medical records from births between Jan 1, 1990, and May 31, 2002, disability records from 1965 to 1997, and retinal examinations from deaf students born between 1985 and 1994, applying the WHO definition for a clinically confirmed case of congenital rubella syndrome. We also reviewed disability data for evidence of epidemic periodicity and estimated yearly incidence of the syndrome from congenital cataract data for births between 1990 and 2001. FINDINGS: We identified 62 clinically confirmed cases of congenital rubella syndrome from medical records, 148 from disability records, and 15 in deaf students. We noted no epidemic periodicity in disability data, and estimated a yearly incidence of the syndrome in Morocco of 8.1-12.7 cases per 100000 livebirths. INTERPRETATION: We show evidence of congenital rubella syndrome in Morocco and support the addition of rubella vaccination to the national programme. Various data sources can be explored to rapidly assess burden of the syndrome; ophthalmology departments and outpatient cardiology clinics could offer the most potential for such case finding, dependent on documentation practices.

Evidence of clinical and genetic heterogeneity in autosomal dominant congenital cerulean cataracts.

Autosomal dominant cerulean cataracts (ADCC) have previously been mapped to two loci: one on chromosome 17q24 and the other on chromosome 22q11.2-q12.2, which includes the beta-B2 crystallin (CRYBB2) candidate gene. Using polymorphic markers in these regions (D17S802, D17S836, D17S1806 and CRYBB2, D22S258) for linkage analysis, we excluded these loci in a large Moroccan family presenting with an unusual form of ADCC with early onset of lens opacities and rapid evolution. This finding confirms the clinical and genetic heterogeneity of autosomal dominant congenital cerulean cataracts.