Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause cardiomyopathy and heart failure. These mutations were described in the mt-tRNA genes and in the mitochondrial protein-coding genes. The aim of this study was to identify the genetic defect in two patients belonging to two families with cardiac dysfunction associated to a wide spectrum of clinical phenotypes. The sequencing analysis of the whole mitochondrial DNA in the two patients and their parents revealed the presence of known polymorphisms associated to cardiomyopathy and two pathogenic mutations in DNA extracted from blood leucocytes: the heteroplasmic m.3243A > G mutation in the MT-TL1 gene in patient A; and the homoplasmic m.5182C > T mutation in the ND2 gene in patient B. Secondary structure analysis of the ND2 protein further supported the deleterious role of the m.5182C > T mutation, as it was found to be involved an extended imbalance in its hydrophobicity and affect its function. In addition, the mitochondrial variants identified in patients A and B classify both of them in the same haplogroup H2a2a1.

Background: Data reported from several countries show that both children and adolescents accounted for less than 2% of symptomatic cases of Coronavirus disease 2019 (COVID-19). The study objective was to describe the clinical characteristics of children admitted to Tunisian paediatric intensive care units (PICU). Methods: This was a single centre observational retrospective study conducted in the PICU of the Farhat Hached tertiary teaching hospital in Sousse, Tunisia during the period from the March 1, 2020 to February 28, 2022. We included all children aged from one month to 15 years with recent severe or critical severe acute respiratory syndrome coronavirus 2. Infection was confirmed by the positivity of reverse transcriptase either for SARS-CoV2 or with presence of IgM antibodies. We included severe and critical forms of COVID-19 according to the World Health Organization (WHO) classification. Results: 26 patients were included. 16 (61%) were one year old or younger. 18 patients (69.2%) were male. The median age in our research series was six months [1-156 months]. 17 (65.3%) patients had morbidities including mainly cardiac and neurological diseases. Fever (88.4%) and tachypnea (80.8%) were the most common clinical signs. Leukocytosis, high level of C-reactive protein, D-dimer, troponin, and pro-B type natriuretic peptide levels were found in 17, 8, 10, 6, and 10 cases respectively. Seven patients were initially treated with high-flow nasal cannula and didn't need escalation. Three were intubated. Invasive mechanical ventilation was used in six cases. Antibiotics and corticosteroids were used in 84% and 42.3% of children. The median paediatric intensive care unit length-of-stay was 10.9 days. There were six deaths. Conclusion: Paediatricians should be vigilant to the different clinical manifestations of COVID-19 in children admitted in PICU. Special attention should be allocated to infants under one year of age, of the male gender, and for children with comorbidities.

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Background: Lissencephaly represents a rare subgroup of genetically distinct neurological disorders of neuronal migration characterized by a paucity or absence of cerebral gyration. The most common form of lissencephaly has been isolated and referred to as classic or type 1 lissencephaly. It is frequently related to abnormalities within LIS1 or DCX genes, with abnormalities ranging from single base pair substitutions to contiguous gene deletions. Methods: In this study, we report, for the first time, a clinical and genetic characterization of eight unrelated Tunisian children presenting type 1 lissencephaly. We screened LIS1 and DCX abnormalities thanks to a combination of molecular cytogenetic methods and next generation sequencing. Results: One deletion of DCX and three deletions of LIS1 were observed. One of these deletions was inherited from a maternal reciprocal translocation and estimated to approximately 2,9 Mb length. In addition, a 26 Kb LIS1 deletion was detected and refined between exon 3 up to exon 11 by target capture and sequencing. The last LIS1 rearrangement was a mutation (c.779T>A, p.V260E). Finally, two novel DCX mutations were found out (c.910G>C, p.G304R/c.436T>C, p.F146L). Conclusions: Our data confirm the individuality and originality of type 1 lissencephaly on both the phenotypic and the genetic levels. Furthermore, our data confirm again that LIS1 and DCX are the most genes associated with type 1 lissencephaly and spotlight the usefulness of developing approaches and methods for detecting a large number of known causative gene mutations.