Jaber Lyahyai

Spinal muscular atrophy carrier frequency and estimated prevalence of the disease in Moroccan newborns.

Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases caused by homozygous deletion of exon 7 of the survival motor neuron 1 (SMN1) gene in approximately 95% of SMA patients. Carrier frequency studies of SMA have been reported for various populations. The aim of our study was to estimate the carrier frequency of the common SMN1 exon 7 deletion in the Moroccan population to achieve an insight into the prevalence of SMA in Morocco. In this study, we used a reliable quantitative real-time polymerase chain reaction assay with SYBR Green I dye to determine the copy number of the SMN1 gene. Analysis of 150 Moroccan newborns predicts a carrier frequency of approximately 1:25, which would mean a calculated SMA prevalence of 1:1800 after correction due to consanguinity. These results show as expected that the SMA carrier frequency in Morocco is higher than in the European populations and is close to those of Middle Eastern countries. Genetic carrier testing for genetic counseling should be recommended particularly to families with a clear clinical history of SMA.

Further evidence for causal FAM20A mutations and first case of amelogenesis imperfecta and gingival hyperplasia syndrome in Morocco: a case report

BackgroundAmelogenesis imperfecta represents a group of developmental conditions, clinically and genetically heterogeneous, that affect the structure and clinical appearance of enamel. Amelogenesis imperfecta occurred as an isolated trait or as part of a genetic syndrome. Recently, disease-causing mutations in the FAM20A gene were identified, in families with an autosomal recessive syndrome associating amelogenesis imperfecta and gingival fibromatosis.Case presentationWe report, the first description of a Moroccan patient with amelogenesis imperfecta and gingival fibromatosis, in whom we performed Sanger sequencing of the entire coding sequence of FAM20A and identified a homozygous mutation in the FAM20A gene (c.34_35delCT), already reported in a family with this syndrome.ConclusionOur finding confirms that the mutations of FAM20A gene are causative for amelogenesis imperfecta and gingival fibromatosis and underlines the recurrent character of the c.34_35delCT in two different ethnic groups.

Identification of two novel SH3PXD2B gene mutations in Frank-Ter Haar syndrome by exome sequencing: Case report and review of the literature

BACKGROUND Frank-Ter Haar syndrome (FTHS) is an autosomal-recessive disorder characterized by skeletal, cardio-vascular, and eye abnormalities, such as increased intraocular pressure, prominent eyes, and hypertelorism. The most common underlying genetic defect in Frank-Ter Haar syndrome appears to be due to mutations in the SH3PXD2B gene on chromosome 5q35.1. Until now, only six mutations in SH3PXD2B gene have been identified. A genetic heterogeneity of FTHS was suggested in previous studies. DESIGN FTHS was suspected clinically in a girl of 2years old, born from non-consanguineous Moroccan healthy parents. The patient had been referred to a medical genetics outpatient clinic for dysmorphic facial features. Whole Exome Sequencing (WES) was performed in the patient and her parents, in addition to Sanger sequencing that was carried out to confirm the results. RESULTS We report the first description of a Moroccan FTHS patient with two novel compound heterozygous mutations c.806G>A; p.Trp269* (maternal allele) and c.892delC; p.Asp299Thrfs*44 (paternal allele) in the SH3PXD2B gene. Sanger sequencing confirmed this mutation in the affected girl and demonstrated that her parents carry this mutation in heterozygous state. CONCLUSION Our results confirm the clinical diagnosis of FTHS in this reported family and contribute to expand the mutational spectrum of this rare disease. Our study shows also, that exome sequencing is a powerful and a cost-effective tool for the diagnosis of a supposed genetically heterogeneous disorder such FTHS.

Next Generation Sequencing identifies mutations in GNPTG gene as a cause of familial form of scleroderma-like disease.

BackgroundScleroderma 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.MethodsThree 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.ResultsMutation 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.ConclusionOur 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.

Novel DDR2 mutation identified by whole exome sequencing in a Moroccan patient with spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type

Spondylo‐meta‐epiphyseal dysplasia (SMED), short limb‐abnormal calcification type (SMED, SL‐AC), is a very rare autosomal recessive disorder with various skeletal changes characterized by premature calcification leading to severe disproportionate short stature. Twenty‐two patients have been reported until now, but only five mutations (four missense and one splice‐site) in the conserved sequence encoding the tyrosine kinase domain of the DDR2 gene has been identified. We report here a novel DDR2 missense mutation, c.370C > T (p.Arg124Trp) in a Moroccan girl with SMED, SL‐AC, identified by whole exome sequencing. Our study has expanded the mutational spectrum of this rare disease and it has shown that exome sequencing is a powerful and cost‐effective tool for the diagnosis of clinically heterogeneous disorders such as SMED.

Exome sequencing reveals a novel PLP1 mutation in a Moroccan family with connatal Pelizaeus-Merzbacher disease: a case report

BackgroundEpilepsy 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 presentationKnowing 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.ConclusionThis report extends the spectrum of PLP1 mutations and highlights the diagnostic utility of NGS to investigate this group of heterogeneous disorders.

20p12.3 deletion is rare cause of syndromic cleft palate: case report and review of literature

AbstractBackgroundOrofacial cleft (OFC) is one of the most common congenital malformations with a global incidence of approximately 1/700 live births. Clinically, OFCs can be syndromic or non-syndromic.Case presentationA 5 years old boy admitted for genetic evaluation because of psychomotor delay, failure to thrive, dysmorphic features and cleft palate. Conventional cytogenetic showed a notably short p arm of one chromosome 20. FISH analysis identified the derivative chromosome 20 as a de novo 20p12.3 deletion.ConclusionWe present in this paper a Moroccan patient with syndromic cleft palate caused by a de novo 20p12.3 deletion, and we highlight the interest of FISH in the diagnosis confirmation of chromosomal rearrangement. In practice, 20p12.3 deletion should be considered as an etiological diagnosis in the case of syndromic cleft palate.

Correction to: Exome sequencing reveals a novel PLP1 mutation in a Moroccan family with connatal Pelizaeus-Merzbacher disease: a case report

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.