A novel SCN8A variant of unknown significance in pediatric epilepsy: a case report.

Variants in SCN8A are associated with several diseases, including developmental and epileptic encephalopathy, intermediate epilepsy or mild-to-moderate developmental and epileptic encephalopathy, self-limited familial infantile epilepsy, neurodevelopmental delays with generalized epilepsy, neurodevelopmental disorder without epilepsy, hypotonia, and movement disorders. Herein, we report an 8-year-old Moroccan boy with intermediate epilepsy of unknown origin, intellectual disability, autism spectrum disorder, and hyperactivity. The patient presented a normal 46, XY karyotype and a normal comparative genomic hybridization profile. Whole-exome sequencing was performed, and heterozygous variants were identified in KCNK4 and SCN8A. The SCN8A variant [c.4499C > T (p.Pro1500Leu)] was also detected in the healthy mother and was classified as a variant of uncertain clinical significance. This variant occurs in a highly conserved domain, which may affect the function of the encoded protein. More studies are needed to confirm the pathogenicity of this novel variant to establish the effective care, management, and genetic counselling of affected individuals.

R306X Mutation in the MECP2 Gene Causes an Atypical Rett Syndrome in a Moroccan Patient: A Case Report.

Rett syndrome (RTT) is a rare X-linked syndrome that predominantly affects girls. It is characterized by a severe and progressive neurodevelopmental disorder with neurological regression and autism spectrum features. The Rett syndrome is associated with a broad phenotypic spectrum. It ranges from a classical Rett syndrome defined by well-established criteria to atypical cases with symptoms similar to other syndromes, such as Angelman syndrome. The first case of a Moroccan female child carrying a R306X mutation in the MECP2 (Methyl-CpG-Binding Protein 2) gene, with an unusual manifestation of Rett syndrome, is presented here. She showed autistic regression, behavioral stagnation, epilepsy, unmotivated laughter, and craniofacial dysmorphia. Whole exome sequencing revealed a nonsense mutation (R306X), resulting in a truncated, nonfunctional MECP2 protein. The overlapping phenotypic spectrums between Rett and Angelman syndromes have been described, and an interaction between the MECP2 gene and the UBE3A (Ubiquitin Protein Ligase E3A) gene pathways is possible but has not yet been proven. An extensive genetic analysis is highly recommended in atypical cases to ensure an accurate diagnosis and to improve patient management and genetic counseling.

Assessment of phylogenetic structure of Berber-speaking population of Azrou using 15 STRs of Identifiler kit.

Allele frequencies for 15 STR autosomal loci of Identifiler kit (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) in the Moroccan population of Berber-speaking of Azrou, were assessed from a sample of 201 unrelated individuals. Markers D18S51, D2S1338, FGA and D21S11 present the highest power of discrimination (PD) values while D21S11 was the most polymorphic locus in the studied population. The phylogenetic tree established among worldwide populations, shows that Berber-speaking population of Azrou was so close to the Berber-speaking population of Asni but also to the Arab-speaking population of southern Morocco. Nevertheless, a significant distance was observed between populations of Azrou and Bouhria even they share the same dialect (Amazigh) and belong to the same geographical area (Morocco). The 15 STR loci studied appear to be highly discriminating, thus providing a powerful tool for forensic applications, paternity investigation, individual identification and anthropological studies.

Autosomal recessive and sporadic deafness in Morocco: high frequency of the 35delG GJB2 mutation and absence of the 342-kb GJB6 variant.

Deafness is a heterogeneous disorder showing different pattern of inheritance and involving a multitude of different genes. Mutations in the gene, GJB2 Gap junction type 1), encoding the gap junction protein connexin-26 on chromosome 13q11 may be responsible for up 50% of autosomal recessive nonsyndromic hearing loss cases (ARNSHL), and for 15-30% of sporadic cases. However, a large proportion (10-42%) of patients with GJB2 has only one GJB2 mutant allele. Recent reports have suggested that a 342-kb deletion truncating the GJB6 gene (encoding connexin-30), was associated with ARNSHL through either homozygous deletion of Cx30, or digenic inheritance of a Cx30 deletion and a Cx26 mutation in trans. Because mutations in Connexin-26 (Cx26) play an important role in ARNSHL and that distribution pattern of GJB2 variants differs considerably among ethnic groups, our objective was to find out the significance of Cx26 mutations in Moroccan families who had hereditary and sporadic deafness. One hundred and sixteen families with congenital deafness (including 38 multiplex families, and 78 families with sporadic cases) were included. Results show that the prevalence of the 35delG mutation is 31.58% in the family cases and 20.51% in the sporadic cases. Further screening for other GJB2 variants demonstrated the absence of other mutations; none of these families had mutations in exon 1 of GJB2 or the 342-kb deletion of GJB6. Thus, screening of the 35delG in the GJB2 gene should facilitate routinely used diagnostic for genetic counselling in Morocco.