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Abstract Background Wolfram syndrome is a rare autosomal recessive neurodegenerative disorder that affects 1/200,000 to 1/1,000,000 children. It is characterized by juvenile onset diabetes, optic nerve atrophy and other systemic manifestations. Symptoms of the disease arise mostly in early childhood with a high mortality rate due to severe neurological complications. Two causative genes have been identifed in this syndrome; the classical form is caused by autosomal recessive mutations of the WFS1 gene, and a smaller portion of patients has mutations in the CIDS2 gene, which are responsible for autosomal recessive Wolfram syndrome 2. Case presentation We report the case of a 28-year-old Moroccan boy born from consanguineous parents referred to the department of medical genetics at the National Institute of Health in Rabat. The diagnosis of Wolfram syndrome was made based on insulin-dependent diabetes, optic nerve atrophy, sensorineural deafness, urological abnormalities and psychiatric illness. To establish the diagnosis at a molecular level, we performed next-generation sequencing in the index patient, which revealed compound heterozygous WFS1 mutations: c.1113G > A (p.Trp371Ter) and c.1223_1224insGGAACCACCTGGAGCCCTATGCCCATTT (p.Phe408fs). This second variant has never been described in patients with Wolfram syndrome. Conclusion The identification of the genetic substrate in our patient confirmed the clinical diagnosis of Wolfram syndrome and allowed us to provide him an appropriate management and genetic counseling to his family.

Abstract Background Wilson disease is a rare autosomal recessive disorder characterized by toxic accumulation of copper in various organs, principally in the liver and brain. The disease can be manifested with hepatic, neurologic and ophthalmic signs and in a rare case with psychiatric, hematological, renal and skeletal signs; symptoms vary among and within families. Traditionally, Wilson disease was diagnosed on the basis of biochemical markers which include low ceruloplasmin levels and elevated urinary and hepatic copper. However, theses parameters are not specific and can been seen in other disorders. Genetic testing is now considering the most specific test allowing a precise diagnosis. In this study, we report the results of molecular analysis of four unrelated patients with Wilson disease from Morocco; we used a next-generation sequencing customized multigene panel to investigate the ATP7B gene for the four unrelated patients with Wilson disease. Results Genetic tests based on next-generation sequencing allow to the identification of four previously described variants. One in compound heterozygous state and three at homozygous state. Conclusions Our results confirm the clinical diagnosis of Wilson disease in these reported families and have implications for their genetic counselling and clinical management. Diagnosis of Wilson disease is a major challenge in clinical practice, and Genetic testing of ATP7B gene should be recommended in patients with suspected Wilson disease.

Introduction: The majority of small supernumerary marker chromosomes (sSMCs) are derived from one single chromosome. Complex sSMCs, on the other hand, consist of genetic material derived from more than one, normally two chromosomes. Complex sSMCs involving chromosomes 8 and 14 are rarely encountered.Case presentation: We present here a 14-month-old boy born from an unrelated couple. At birth, the baby was hypotonic and had a cleft lip and palate, as well as ocular involvement. Throughout the course of development, the baby experienced feeding difficulties, stunted growth, and delayed psychomotor development. Banding together with molecular cytogenetics revealed a balanced maternal translocation t(8;14)(p22.3;q21)mat, leading due to meiotic 3:1 segregation to a partial trisomy of chromosomes 8 and 14 in the affected boy.Discussion/Conclusion: This report highlights the importance of cytogenetics in diagnosis of rare genetic disorders, with impact on genetic counselling of patients and their families. There are three comparable cases in the literature involving both chromosomes 8 and 14, but with different breakpoints; the complex sSMC derived from chromosomes 8 and 14 in this case, characterized as der(14)t(8;14) (p22.3;q21)mat.

Abstract Background Congenital muscular dystrophies (CMD) and congenital myopathies (CM) are clinically and genetically heterogeneous groups of neuromuscular disorders resulting in prenatal or early-onset hypotonia, muscle weakness, myogenic pattern, and dystrophic or myopathic features on muscle biopsy. In this study, we provide a genetic and molecular characterization of CMD and CM in Moroccan patients. Patients and methods In this cohort, we investigated 23 Moroccan patients from 21 families who consented to genetic testing. Firstly, genetic analysis in the probands was conducted by next-generation sequencing (NGS) technology using two approaches: targeted NGS gene panel and clinical exome sequencing to study the mutational spectrum and to achieve an accurate diagnosis of these hereditary myopathies in Morocco. Results NGS data analysis revealed 16 pathogenic variants harbored in 17 unrelated patients that were genetically resolved. The phenotypic forms identified were in order: LAMA2-related CMD (52.94%), LMNA-CMD (23.53%), and RYR1-related congenital myopathy (17.65%). The congenital titinopathy group was less frequent (5.88%). Here, we identified two novel recessive variants in LAMA2 gene: c.2164G > A (p.Glu722Lys), and c.(6992 + 1_6993-1)_(7300 + 1_7301-1)del p.(Pro2332Glnfs*10). Additionally, we expanded the phenotypic spectrum of a known heterozygous LMNA c.1718C > T p.(Ser573Leu) variant, and we report it for the first time to a form of CMD. Conclusions The introduction of the NGS tool in clinical practice allowed us to improve the diagnosis and the management of these neuromuscular diseases and to highlight the importance of molecular genetic diagnosis of these disorders that are underestimated in the Moroccan population.

Abstract Background Congenital myasthenic syndromes (CMSs) are rare genetic diseases due to abnormalities of the neuromuscular junction leading to permanent or transient muscle fatigability and weakness. To date, 32 genes were found to be involved in CMSs with autosomal dominant and/or recessive inheritance patterns. CMS with acetylcholinesterase deficiency, in particular, was determined to be due to biallelic mutations of COLQ gene with early-onset clinical signs. Here, we report clinical features and novel molecular findings of COLQ-related CMS in a Moroccan patient with a review of the literature for this rare form. Case presentation In this study, we report the case of a 28-month-old Moroccan female patient with hypotonia, associated to axial muscle weakness, global motor delay, bilateral ptosis, unilateral partial visual field deficiency with normal ocular motility, and fatigable muscle weakness. Clinical exome sequencing revealed a novel homozygous deletion of exon 13 in COLQ gene, NM_005677.4(COLQ):c.(814+1_815-1)_(954+1_955-1) del p.(Gly272Aspfs*11). This finding was subsequently confirmed by quantitative real-time PCR (qPCR) in the proband and her parents. In silico analysis of protein-protein interaction network by STRING tool revealed that 12 proteins are highly associated to COLQ with an elevated confidence score. Treatment with Salbutamol resulted in clear benefits and recovery. Conclusions This clinical observation illustrates the important place of next-generation sequencing in the precise molecular diagnosis of heterogeneous forms of CMS, the appropriate management and targeted treatment, and genetic counseling of families, with a better characterization of the mutational profile of this rare disease in the Moroccan population.

Abstract Native plants in extreme environments may harbor some unique microbial communities with particular functions to sustain their growth and tolerance to harsh conditions. The aim of this study was to investigate the bacterial communities profiles in some native plants and samples of the Moroccan phosphate mine ecosystem by assessing the percentages of taxonomic identification using six hypervariable regions of the 16S rRNA. The rhizosphere of the three wild plants in the Moroccan phosphate mine is characterized by interesting bacterial diversity including Proteobacteria (62.24%, 71.15% and 65.61%), Actinobacteria (22.53%, 15.24%, 22.30%), Bacteroidetes (7.57%; 4.23%; 7.63%), and Firmicutes (5.82%; 1.17%; 2.83%). The bulk phosphate mine samples were dominated by Actinobacteria with average relative abundance of 97.73% that are different from those inferred in the rhizosphere samples of the native plants. The regions V3, V4 and V67 performed better in the taxonomic profiling at different taxonomic levels. Results indicated that both plant genotype and mainly soil conditions may be involved in the shaping of bacterial diversity. Such indication was also confirmed by the prediction of functional profiles that showed enrichment of many functions related to biological nitrogen fixation in the rhizosphere of native plants and the stress related functions in the bulk phosphate mine in comparison with the wheat rhizosphere samples.

Abstract Background 15q26 deletion is a relatively rare chromosomal disorder, and it is described only in few cases. Patients with this aberration show many signs and symptoms, particularly pre- and postnatal growth restriction, developmental delay, microcephaly, intellectual disability and various congenital malformations. Case presentation We report on a girl, 4 years old, of consanguineous parents, with a 15q26 deletion. Clinical manifestations included failure to thrive, developmental delay, microcephaly, dysmorphic facies with broad forehead, hypertelorism, narrowed eyelid slits and protruding columella. The patient also showed skeletal abnormalities, especially clinodactyly of the 5th finger, varus equine right foot and left club foot. Additionally, she had teething delay and divergent strabismus. Heart ultrasound displayed two atrial septal defects with left-to-right shunt, enlarging the right cavities. Routine cytogenetic analysis revealed a shortened 15q chromosome. Subsequent array analysis disclosed a terminal 9.15 Mb deletion at subband 15q26.1-q26.3. Four candidate genes associated with 15q26 deletion phenotype were within the deleted region, i.e. IGF1R, NR2F2, CHD2 and MEF2A. Conclusion We report on an additional case of 15q26 monosomy, characterized by array-CGH. Molecular cytogenetic analysis allowed us to identify the exact size of the deletion, and four candidate genes for genotype-phenotype correlation. 15q26 monosomy should be considered when growth retardation is associated with hearing anomalies and congenital heart defect, especially atrioventricular septal defects (AVSDs) and/or aortic arch anomaly (AAA).

Abstract Background Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a rare autosomal recessive genetic condition caused by deleterious mutations in the LAMA2 gene encoding the laminin-α2 chain. It is the most frequent subtype of congenital muscular dystrophies (CMDs) characterized by total laminin-α2 deficiency with muscle weakness at birth or in the first six months of life. To the best of our knowledge, this study reports the first molecular diagnosis and genetic defect of this heterogeneous form of CMD performed in a Moroccan medical genetic center using next-generation sequencing (NGS). It allows us to expand the mutational spectrum of the LAMA2 gene. Case presentation We report the case of a female Moroccan child with clinical and paraclinical features in favor of a CMD. She has global congenital hypotonia with generalized muscle weakness, psychomotor retardation, increased serum creatine kinase, and normal brain scan at the age of six months. Targeted NGS leads to the identification of a novel homozygous nonsense mutation c.2217G > A, p.(Trp739*) in the exon 16 of LAMA2. Sanger sequencing confirmed this mutation in the affected patient and showed that her parents are heterozygous carriers. Conclusions A modern genetic analysis by NGS improves the genetic diagnosis pathway for adequate genetic counseling of affected families more precisely. An accession number from the National Center for Biotechnology Information (NCBI) ClinVar database was retrieved for this novel LAMA2 mutation.

Abstract 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.

Abstract Background In Morocco, consanguinity rate is very high; which lead to an increase in the birth prevalence of infants with autosomal recessive disorders. Previously, it was difficult to diagnose rare autosomal recessive diseases. Next Generation Sequencing (NGS) techniques have considerably improved clinical diagnostics. A genetic diagnosis showing biallelic causative mutations is the requirement for targeted carrier testing in parents, prenatal and preimplantation genetic diagnosis in further pregnancies, and also for targeted premarital testing in future couples at risk of producing affected children by a known autosomal recessive disease. Methods In this report, we present our strategy to advise a future couple of first cousins, whose descendants would risk cystinosis; an autosomal recessive lysosomal disease caused by mutations in the CTNS gene. Indeed, our future husband’s sister is clinically and biochemically diagnosed with cystinosis in early childhood. First, we opted to identify the patient’s CTNS gene abnormality by using (NGS), then we searched for heterozygosity in the couple’s DNA, which allows us to predict the exact risk of this familial disease in the future couple’s offspring. Results We have shown that the future husband, brother of the patient is heterozygous for the familial mutation. On the other hand, his future wife did not inherit the familial mutation. Therefore, genetic counseling was reassuring for the risk of familial cystinosis in this couple’s offspring. Conclusions We report in this study, one of the major applications of (NGS), an effective tool to improve clinical diagnosis and to provide the possibility of targeted premarital carrier testing in couples at risk.

Abstract Background Epilepsy is the most common neurological disorder that causes spontaneous, unprovoked, and recurrent seizures. Epilepsy is clinically and genetically heterogeneous with various modes of inheritance. The complexity of epilepsy presents a challenge and identification of the causal genetic mutation allows diagnosis, genetic counseling, predicting prognosis, and, in some cases, treatment decisions. Clinical exome sequencing is actually becoming a powerful approach for molecular diagnosis of heterogeneous neurological disorders in clinical practice. Case presentation We report our observations of three unrelated Moroccan patients referred to our genetics department for molecular diagnosis of epilepsy: a 4-year-old Moroccan boy, a 3-year-old Moroccan girl, and a 7-year-old Moroccan boy. Due to the heterogeneity and complexity of epilepsy, we performed clinical exome sequencing followed by targeted analysis of 936 epilepsy genes. A total of three mutations were identified in known epilepsy genes (SCN1A, SCN2A). By clinical exome sequencing, we identified two novel mutations: c.4973C>A (p.Thr1658Lys) in SCN1A gene and c.1283A>G (p.Tyr428Cys) in the SCN2A gene, whereas the third mutation c.3295G>T (p.Glu1099*) was already described in patients with Dravet syndrome. Conclusion This study demonstrates that clinical exome sequencing is an effective diagnosis tool to investigate this group of diseases with huge diversity and defends its use in clinical routine.

Loss of the cadherin FAT1 has been associated with nephropathy and epithelial cell adhesion defects. Here, the authors report five families with a syndromic form of coloboma associated with homozygous frameshift variants in FAT1 and recapitulate the phenotype in mutant mice and zebrafish.

Split-hand foot malformation (SHFM) is a clinically heterogeneous congenital limb defect affecting predominantly the central rays of hands and/or feet. The clinical expression varies in severity between patients as well between the limbs in the same individual. SHFM might be non-syndromic with limb-confined manifestations or syndromic with extra-limb manifestations. Isolated SHFM is a rare condition with an incidence of about 1 per 18,000 live born infants and accounts for 8-17 % of all limb malformations. To date, many chromosomal loci and genes have been described as associated with isolated SHFM, i.e., SHFM1 to 6. SHFM6 is one of the rarest forms of SHFM, and is caused by mutationsin WNT10B gene. Less than ten pathogenic variants have been described. We have investigated a large consanguineous Moroccan family with three affected members showing feet malformations with or without split hand malformation phenotypes. Using an exome sequencing approach, we identified a homozygous nonsense variant p.Arg115*of WNT10B gene retaining thereby the diagnosis of SHFM6.This homozygous nonsense mutation identified by exome sequencing in a large family of split hand foot malformation highlights the importance of exome sequencing in genetically heterogeneous entities.

Abstract Background Pompe disease is an autosomal recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy. Its prevalence ranges between 1/9000 and 1/40,000. It is caused by compound heterozygous or homozygous mutations in the GAA gene, which encodes for the lysosomal enzyme alpha-glucosidase, required for the degrading of lysosomal glycogen. Case presentation In this study, we report the case of a Moroccan consanguineous family with hypertrophic cardiomyopathy and sudden cardiac deaths at an early age; our patient was a 7-month-old Moroccan girl. Whole exome sequencing identified the deleterious homozygous mutation c.236_246delCCACACAGTGC (p.Pro79ArgfsX13) of GAA gene leading to a post-mortem diagnosis of Pompe disease. Conclusion The identification of the genetic substrate in our patient, the daughter, confirmed the clinical diagnosis of Pompe disease and allowed us to provide appropriate genetic counseling to the family for future pregnancies.

Abstract Background Autosomal recessive primary microcephaly (MCPH) is a rare genetically heterogeneous disorder of neurogenic brain development characterized by a reduced head circumference at birth with no remarkable anomalies of brain architecture and variable degrees of intellectual impairment. Clinical and genetic heterogeneity in genetic disorders represent a major diagnostic challenge. Case presentation Two patients, 11 and 9 years old, born from consanguineous parents, were referred to the department of medical genetics at the National Institute of Health in Rabat. The diagnosis of MCPH was made, based on reduced head circumference without brain architecture abnormalities. The two patients were subject to the whole-exome sequencing, which allowed to diagnose a novel homozygous mutation c.1027C > T; p.Gln343* in exon 8 of WDR62, a gene already known to be related to MCPH. Sanger sequencing confirmed the segregation of the mutation in the family. Conclusion Our data expends the spectrum of mutations in WDR62 gene, proves the efficiency and cost-effectiveness of whole exome sequencing for the molecular diagnosis of genetically heterogeneous disorders such MCPH. Exome sequencing led to the rapid and cost-effective identification of a novel homozygous mutation in WDR62 gene, thereby facilitating genetic counseling.

Abstract Background Familial Mediterranean fever is an autoinflammatory disease of unknown etiology, characterized clinically by recurrent attacks of sudden-onset fever with arthralgia and/or thoracoabdominal pain and pathogenetically by autosomal recessive inheritance due to a mutation in the MEFV gene. Behçet’s disease is an inflammatory disease characterized by recurrent oral and genital aphthous ulcerations, uveitis, and skin lesions. Preliminarily, our literature review suggested that patients with familial Mediterranean fever who also have Behçet’s disease have only a single mutated familial Mediterranean fever gene. The MEFV gene mutation responsible for familial Mediterranean fever is probably a susceptibility factor for Behçet’s disease, particularly for patients with vascular involvement, and both disorders can occur concurrently in a patient, as in the present case. Case presentation A 10-year-old girl of Moroccan origin presented to our institution for genetic consultation for genetic testing of the MEFV gene. She had fever associated with abdominal and diffuse joint pain in addition to headache. These symptoms have oriented pediatricians to familial Mediterranean fever. The evolution was marked by Behçet’s syndrome symptoms. Sanger sequencing followed by complete exome sequencing analysis of the MEFV gene for the proband mutation revealed a novel variant. We conclude that the novel single variant c.2078 T > A (p.Met693Lys) could be responsible for the association of familial Mediterranean fever and Behçet’s disease. Conclusion To the best of our knowledge, this is the first report of a new variant in exon 10 of the MEFV gene in a Moroccan family. This novel variant should be listed in the MEFV sequence variant databases.

Abstract Background Epilepsy regroups a common and diverse set of chronic neurological disorders that are characterized by spontaneous, unprovoked, and recurrent epileptic seizures. Epilepsies have a highly heterogeneous background with a strong genetic contribution and various mode of inheritance. X-linked epilepsy usually manifests as part of a syndrome or epileptic encephalopathy. The variability of clinical manifestations of X-linked epilepsy may be attributed to several factors including the causal genetic mutation, making diagnosis, genetic counseling and treatment decisions difficult. We report the description of a Moroccan family referred to our genetic department with X-linked epileptic seizures as the only initial diagnosis. Case presentation Knowing the new contribution of Next-Generation Sequencing (NGS) for clinical investigation, and given the heterogeneity of this group of disorders we performed a Whole-Exome Sequencing (WES) analysis and co-segregation study in several members of this large family. We detected a novel pathogenic PLP1 missense mutation c.251C > A (p.Ala84Asp) allowing us to make a diagnosis of Pelizaeus-Merzbacher Disease for this family. Conclusion This report extends the spectrum of PLP1 mutations and highlights the diagnostic utility of NGS to investigate this group of heterogeneous disorders.

Abstract Background Scleroderma is a multisystem disease, characterized by fibrosis of skin and internal organs, immune dysregulation, and vasculopathy. The etiology of the disease remains unknown, but it is likely multifactorial. However, the genetic basis for this condition is defined by multiple genes that have only modest effect on disease susceptibility. Methods Three Moroccan siblings, born from non-consanguineous Moroccan healthy parents were referred for genetic evaluation of familial scleroderma. Whole Exome Sequencing was performed in the proband and his parents, in addition to Sanger sequencing that was carried out to confirm the results obtained. Results Mutation analysis showed two compound heterozygous mutations c.196C>T in exon 4 and c.635_636delTT in exon 9 of GNPTG gene. Sanger sequencing confirmed these mutations in the affected patient and demonstrated that their parents are heterozygous carriers. Conclusion Our findings expand the mutation spectrum of the GNPTG gene and extend the knowledge of the phenotype–genotype correlation of Mucolipidosis Type III gamma. This report also highlights the diagnostic utility of Next Generation Sequencing particularly when the clinical presentation did not point to specific genes.

Abstract Background To date, a limited number of BRCA1/2 germline mutations have been reported in hereditary breast and/or ovarian cancer in the Moroccan population. Less than 20 different mutations of these two genes have been identified in Moroccan patients, and recently we reported a further BRCA2 mutation (c.1310_1313delAAGA; p.Lys437IlefsX22) in three unrelated patients, all from the North-East of the country. We aimed in this study to evaluate the frequency and geographic distribution of this BRCA2 frameshift mutation, in order to access its use as the first-line BRCA genetic testing strategy for Moroccan patients. We enrolled in this study 122 patients from different regions of Morocco, with suggestive inherited predisposition to breast and ovarian cancers. All subjects gave written informed consent to BRCA1/2 genetic testing. According to available resources of our lab and enrolled families, 51 patients were analyzed by the conventional individual exon-by-exon Sanger sequencing, 23 patients were able to benefit from a BRCA next generation sequencing and a target screening for exon 10 of BRCA2 gene was performed in 48 patients. Results Overall, and among the 122 patients analyzed for at least the exon 10 of the BRCA2 gene, the c.1310_1313delAAGA frameshift mutation was found in 14 patients. Genealogic investigation revealed that all carriers of this mutation shared the same geographic origin and were descendants of the North-East of Morocco. Discussion In this study, we highlighted that c.1310_1313delAAGA mutation of BRCA2 gene is recurrent with high frequency in patients from the North-East region of Morocco. Therefore, we propose to use, in public health strategies, the detection of this mutation as the first-line screening tests in patients with breast and ovarian cancer originated from this region.

Abstract Background Xeroderma pigmentosum is an autosomal recessive inherited disease. The diagnosis is essentially based on clinical findings and the family history. This genodermatosis is genetically heterogeneous; to date, nine genes have been associated to this disorder. Based on the result of many studies, xeroderma pigmentosum complementation group C is the most common form of xeroderma pigmentosum. A founder mutation in the XPC gene was reported in the Maghreb region of northern Africa. According to these findings, the Department of Medical Genetics in Rabat offers molecular diagnosis by screening for the recurrent mutation c.1643_1644delTG which represents 74% of all the probands with xeroderma pigmentosum. Case presentation We describe the case of a 21-year-old Moroccan son of consanguineous parents diagnosed with xeroderma pigmentosum on the basis of sun-exposed skin abnormalities and bilateral ocular involvement. A molecular study led to the identification of a new frameshift insertion of four nucleotides in exon 9. Conclusions To the best of our knowledge, this mutation has not been described. The sequencing of the ninth exon should be proposed as first line molecular analysis for all Moroccan patients with xeroderma pigmentosum.

Diabetic nephropathy (DN) is one of the severe complications of Type-2 diabetes mellitus (T2DM) and a major cause of end-stage renal disease in these patients. Results from published studies on the relationship between angiotensin-converting enzyme (ACE) insertion/ deletion (I/D) gene polymorphism and patients with DN are still conflicting. We compared the clinical characteristics and the genotype frequencies of ACE polymorphism in 130 T2DM Moroccan patients with DN and 85 T2DM Moroccan patients without DN (controls) using specific primers in a polymerase chain reaction. The degenerative complications of diabetes were significantly higher in the group with nephropathy. The distribution of the I/D genotypes was in Hardy–Weinberg equilibrium. The D allele was the most frequent allele in the Moroccan population in both groups studied (P = 0.68), however, there was no significant difference between the genotypes in T2DM patients with or without DN (P = 0.78). The ACE gene I/D polymorphism was not associated with an increased risk of DN in the Moroccan population.

Background: In Algeria, the data on infertility and its various causes are rare. Recently, the introduction of assisted reproduction has allowed expecting that 300000 couples, which represent 7% of couples of reproductive age, face difficulty conceiving a child. Knowing that most idiopathic cases are likely to be due to chromosomal abnormalities, we aimed to investigate genetic defects by karyotype analysis in Algerian infertile men, using peripheral blood lymphocytes.Methods: A cytogenetic study was conducted on 10 men from infertile couples by Karyotype analysis of R-banding performed by lymphocyte culture technique. Fluorescence in situ hybridization was performed and molecular abnormalities were investigated by polymerase chain reaction. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels were evaluated by immunoradiometric method.Results: Chromosomal abnormalities were observed in 30% of the patients. We identified a homogenous Klinefelter syndrome patient with 47, XXY karyotype, a mosaic Klinefelter syndrome patient with 47, XXY/46, XY karyotype and a 46, XX male. Fluorescence in situ hybridization showed that the sex-determining region Y was translocated to the short arm of the X chromosome in patient with 46, XX chromosomal constitution and the presence of the SRY gene was confirmed by polymerase chain reaction and electrophoresis.Conclusion: The occurrence of chromosomal abnormalities in 30% of the infertile men strongly supports the inclusion of routine cytogenetic testing for diagnostic establishment and suitable counseling for couples seeking for assisted reproduction technologies. Keywords: Male infertility, Cytogenetic, Azoospermia, Severe oligozoospermia

Sanjad-Sakati syndrome (SSS) or hypoparathyroidism-retardation-dysmorphism syndrome (HDR) is a rare autosomal recessive disorder. It is characterized by the association of congenital hypothyroidism, growth retardation, psychomotor retardation, epilepsy, dysmorphic features (microcephaly, facial, eye, and dental anomalies), and abnormalities of the extremities. The prevalence of SSS is unknown. Reported patients are were almost exclusively from the Arabian Peninsula. They are were all homozygous for the ancestral mutation c.155- 166del of the TBCE gene, also known as “the Bedouin mutation.” We report on the first clinical and molecular description of a Moroccan patient with Sanjad-Sakati syndrome. He is was a carrier for the Bedouin mutation, not surprising, knowing that part of the Moroccan population has Arabian origin. This diagnosis allowed us to provide an appropriate management to the patient, to make a genetic counseling to his family, and to enrich genetic data on the Moroccan population.

After publication of the original article [1] it was brought to our attention that author Bouchra Ouled Amar Bencheikh was incorrectly included as Bouchra Oulad Amar Bencheikh.

Myotonia congenita is a genetic muscle disorder characterized by clinical and electrical myotonia, muscle hypertrophy, and stiffness. It is inherited as either autosomal-dominant or -recessive, known as Thomsen and Becker diseases, respectively. These diseases are distinguished by the severity of their symptoms and their patterns of inheritance. Becker disease usually appears later in childhood than Thomsen disease and causes more severe muscle stiffness and pain. Mutations in the muscular voltage-dependent chloride channel gene (CLCN1), located at 7q35, have been found in both types. We report here the case of a Moroccan consanguineous family with a myotonic autosomal-recessive condition in two children. The molecular studies showed that the patients reported here are homozygous for mutation p.Gly482Arg in the CLCN1 gene. The parents were heterozygote carriers for mutation p.Gly482Arg. This diagnosis allowed us to provide an appropriate management to the patients and to make a genetic counselling to their family.

Le syndrome de Silver Russell (SSR) est une maladie génétique rare. Sa prévalence estimée à 1/100.000. Il s'agit d'une pathologie de l'empreinte parentale, caractérisée par une grande diversité phénotypique. Ses signes cliniques majeurs sont: un retard de croissance intra-utérin sévére, un retard staturo-pondéral post natal, une dysmorphie cranio-faciale particuliére et une asymétrie des membres. Nous rapportons dans ce travail les observations de trois patients, qui présentent un retard staturo-pondéral, une dysmorphie faciale caractéristique du SSR et une hemihypertrophie corporelle. Nous discutons à travers ces cas les aspects cliniques et génétiques de ce rare syndrome.

INTRODUCTION: Le but de cette étude était de présenter les premiers résultats de diagnostic anténatal de la trisomie 21 par la technique d'hybridation in situ en fluorescence (FISH) au Maroc et discuter son intérêt dans le diagnostic rapide de cette aneuploïdie. METHODES: Ce travail a été réalisé chez 23 femmes avec des grossesses à haut risque de trisomie 21. La moyenne d'âge des gestantes étaient de 37,43 ans avec des extrêmes de 21 et 43 ans. Toutes étaient musulmanes mariées, mariage légitimé par la Charia, dont trois mariages consanguins, sauf une originaire de la République Démocratique du Congo qui était chrétienne et concubine. La majorité des femmes étaient fonctionnaires et avaient un niveau de scolarisation moyen à élevé. Toutes les patientes ont bénéficié d'une consultation de génétique médicale au cours de laquelle il leur a été donné des informations sur la technique, son intérêt et ses limites. Il s'agit de femmes enceintes qui avaient soit un âge maternel élevé ou des signes d'appel échographiques et/ ou biochimiques. Une des patientes était porteuse d'une translocation robertsonienne t(14;21) équilibrée. Une amniocentèse a été réalisée chez toutes les gestantes et aucun avortement n'a était induit par ce geste invasif. L'âge gestationnel moyen à la première consultation était de 14 semaines d'aménorrhée (SA) et à l'amniocentèse était de 16 SA et 5 jours. L'analyse FISH a été réalisée, après consentement des couples, sur des cellules non cultivées à partir des échantillons de liquides amniotiques, en utilisant des sondes spécifiques du chromosome 21. RESULTATS: Parmi les 23 patientes qui ont bénéficiées d'un diagnostic anténatal de la trisomie 21 par la technique FISH, nous avons pu rassurer 21 d'entre elles, et nous avons détecté deux cas de trisomie 21 fœtal. CONCLUSION: la technique FISH permet un diagnostic anténatal rapide, en moins de 48h, de la trisomie 21 sur une faible quantité de liquide amniotique. Elle offre aux couples l'avantage de prendre, dans des délais raisonnables, la décision qui leur convient concernant la poursuite ou non de la grossesse. Elle permet souvent, avec un résultat normal, de rassurer rapidement les femmes enceintes trop angoissées.

Le syndrome de Costello appelé également syndrome Facio-cutanéo-squelettique est une anomalie rare du développement d'origine génétique de transmission autosomique dominante. Sa prévalence est inconnue mais environ 250 cas ont été rapportés dans la littérature. La majorité des cas sont sporadiques. Les principaux signes sont une dysmorphie faciale caractéristique, un retard mental, un retard de croissance, un cutis laxa, une malformation cardiaque et des papillomes péri-orificiels. Sur le plan génétique, ce syndrome est dû à des mutations au niveau du gène HRAS qui est un oncogène de la famille Ras. Ceci est à l'origine de la prédisposition de ces patients au développement de tumeurs malignes. Le pronostic dépend de la sévérité de la cardiopathie et de la survenue de tumeurs malignes. Les principaux diagnostics différentiels incluent le syndrome de Noonan et le syndrome cardio-facio-cutané. Nous rapportons dans ce travail, une patiente âgée de 13 ans qui présente des signes cliniques du syndrome de Costello. L'analyse moléculaire du gène HRAS a mis en évidence la mutation c.34G>A; p.Gly12Ser de novo au niveau de l'exon 1 de ce gène. Nous montrons à travers cette observation l'intérêt de l'étude moléculaire pour confirmer le diagnostic du syndrome de Costello et pour le conseil génétique de la famille.