Noonan syndrome is a common autosomal dominant disorder characterized by short stature, congenital heart disease and facial dysmorphia with an incidence of 1/1000 to 2500 live births. Up to now, several genes have been proven to be involved in the disturbance of the transduction signal through the RAS-MAP Kinase pathway and the manifestation of Noonan syndrome. The first gene described was PTPN11, followed by SOS1, RAF1, KRAS, BRAF, NRAS, MAP2K1, and RIT1, and recently SOS2, LZTR1, and A2ML1, among others. Progressively, the physiopathology and molecular etiology of most signs of Noonan syndrome have been demonstrated, and inheritance patterns as well as genetic counseling have been established. In this review, we summarize the data concerning clinical features frequently observed in Noonan syndrome, and then, we describe the molecular etiology as well as the physiopathology of most Noonan syndrome-causing genes. In the second part of this review, we assess the mutational rate of Noonan syndrome-causing genes reported up to now in most screening studies. This review should give clinicians as well as geneticists a full view of the molecular aspects of Noonan syndrome and the authentic prevalence of the mutational events of its causing-genes. It will also facilitate laying the groundwork for future molecular diagnosis research, and the development of novel treatment strategies.

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Root-nodulating bacteria were isolated and characterized from grain and forage legumes growing in Fez regions. A total of 110 Rhizobium strains were characterized on the basis of morphological, cultural, and phenotypical properties. Phenotypic characteristics studied included growth rates in various media, colony morphology, tolerances to extremes of temperature, salt and pH and resistance to different concentrations of heavy metals and antibiotics. The isolates were very diverse phenotypically. Eighty seven of isolates were fast growing rhizobia. Thirty four strains tolerated high concentration of salt (2% NaCl). The majority of our isolates tolerated temperatures ranging between 20 and 37°C, but not above 55°C. Also, the isolated strains tolerated extreme pH in their medium from 4.8 to 8.8. The antibiotic resistance of these strains showed a high level of resistance against streptomycin, kanamycin, ampicillin, tetracycline, and chloramphenicol. The highest resistance to heavy metals was recorded for arsenate, copper, zinc, nickel, and mercury. Also, a moderate resistance was found for chromium. Polymerase chain reaction (PCR) method and 16S rRNA gene sequencing were used for the genotypic analysis of 17 Rhizobium strains selected on the basis of phenotypic study. The results showed a high diversity among the strains.

BackgroundTetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect (CHD) with an incidence of 1/3600 live births. This disorder was associated with mutations in the transcription factors involved in cardiogenesis, like Nk2 homeobox5 (NKX2-5), GATA binding protein4 (GATA4) and T-BOX1 (TBX1). GATA4 contributes particularly to heart looping and differentiation of the second heart field.ObjectivesThe aim of this study was to screen a Moroccan cohort with tetralogy of Fallot for GATA4 mutations, and to assess environmental risk factors that could be involved in the occurrence of this disorder.MethodsThirty-one non-syndromic TOF patients, enrolled between 5th April 2014 and 18th June 2015, were screened for GATA4 mutations using direct sequencing of GATA4 coding exons. Statistical assessment of different risk factors, which is a retrospective study, was carried out using Chi-square and Fisher's exact tests.ResultsWe identified seven exonic variants in nine patients (two missense and five synonymous variants); in addition of eight intronic variants. Assessment of environmental risk factors shows significant association of maternal passive smoking with TOF in the Moroccan population.ConclusionThe present study allowed, for the first time, the molecular and environmental characterisation of Moroccan TOF population. Our findings emphasise particularly the strong association of passive smoking with the emergence of tetralogy of Fallot.

Objective:Secundum atrial septal defect (ASDII) has multifactorial etiology that is combination of environmental (e.g., mother’s exposure to toxicity, ethnicity) and genetic causes. Aim of the present study was to screen a Moroccan population with ASDII for NKX2-5 variants and to assess risk factors that may contribute to emergence of the disorder.Methods:Thirty-two non-syndromic ASDII patients were screened for NKX2-5 variants using direct sequencing of polymerase chain reaction-amplified coding regions. Risk factor rates were compared to general population and assessed using Fisher’s exact and chi-square tests. In this retrospective study, criteria of exclusion were suggestive or confirmed syndrome association.Results:Three heterozygous variants were detected in 4 patients. NKX2-5 variant rate in present cohort is estimated to be about 9.4%. Two prominent risk factors in the Moroccan population were highlighted: consanguinity, rate of which was significantly high at 30.8%, and previous maternal miscarriage or sibling sudden death, observed in 34.6% of cohort.Conclusion:Impact of identified variants was discussed and possible disease-predisposing effect is suggested. Findings indicate that ASD may be favored by consanguineous marriage and that NKX2-5 variant rate in ASD patients may be affected by ethnicity. High level of maternal miscarriage and sibling sudden death suggests potential non-sporadic nature as result of putative genetic defect.