Clinical and molecular characterization of myotonia congenita using whole-exome sequencing in Egyptian patients.

BACKGROUND: Myotonia Congenita (MC) is a rare disease classified into two major forms; Thomsen and Becker disease caused by mutations in the CLCN1 gene, which affects muscle excitability and encodes voltage-gated chloride channels (CLC-1). While, there are no data regarding the clinical and molecular characterization of myotonia in Egyptian patients. METHODS: Herein, we report seven Egyptian MC patients from six unrelated families. Following the clinical diagnosis, whole-exome sequencing (WES) was performed for genetic diagnosis. Various in silico prediction tools were utilized to interpret variant pathogenicity. The candidate variants were then validated using Sanger sequencing technique. RESULTS: In total, seven cases were recruited. The ages at the examination were ranged from eight months to nineteen years. Clinical manifestations included warm-up phenomenon, hand grip, and percussion myotonia. Electromyography was performed in all patients and revealed myotonic discharges. Molecular genetic analysis revealed five different variants. Of them, we identified two novel variants in the CLCN1 gene ( c.1583G > C; p.Gly528Ala and c.2203_2216del;p.Thr735ValfsTer57) and three known variants in the CLCN1 and SCN4A gene. According to in silico tools, the identified novel variants were predicted to have deleterious effects. CONCLUSIONS: As the first study to apply WES among Egyptian MC patients, our findings reported two novel heterozygous variants that expand the CLCN1 mutational spectrum for MC diagnosis. These results further confirm that genetic testing is essential for early diagnosis of MC, which affects follow-up treatment and prognostic assessment in clinical practice.

Oxidative Stress and Anti-Oxidant Markers in Premature Infants with Respiratory Distress Syndrome.

BACKGROUND: Neonatal respiratory distress syndrome (RDS) caused by decreased surfactant and structural lung immaturity. The imbalance between oxidative status and antioxidant defence system was suggested to be an important trigger for lung affection with RDS. AIM: The goal of the current research was to elucidate the significance of the oxidant/ antioxidant status in the pathogenesis of RDS in preterm infants. PATIENTS AND METHODS: This controlled study included 31 preterm neonates with RDS and 36 healthy preterm neonates. Quantification level of oxidative stress biomarkers; malondialdehyde (MDA) & hydrogen peroxide (H2O2) along with antioxidant enzymes activity; catalase (CAT) & superoxide dismutase (SOD) in plasma of healthy premature neonates compared with those with RDS. RESULTS: status of oxidative stress markers (MDA & H2O2) showed a significant increase with decreased levels of antioxidant enzymes activity (CAT & SOD) in neonates with RDS when compared to healthy prematures. CONCLUSION: The results obtained in this study indicate that the increased oxidative stress accompanied by reduced antioxidant defences may play a significant role in the pathogenesis of respiratory distress in preterm newborns.

Pentraxin 3: A Potential Novel Predictor for Neonatal Pulmonary Hypertension.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a serious neonatal problem which has a high mortality rate even with advanced modes of mechanical ventilation. Pentraxin 3 is one of the long pentraxins, which plays an essential role in regulation of cell proliferation and angiogenesis. AIM: This study aims to assess serum pentraxin 3 levels in neonates with pulmonary arterial hypertension and compare them in those who have other congenital heart diseases and healthy neonates. Also, we intended to evaluate serum levels of CRP as a mediator of inflammation in the studied groups. METHODS: The study is a case-control study. Cases were recruited from El Galaa Teaching Hospital, classified into three groups; each group had thirty cases. The first one: cases with pulmonary hypertension (PHT), the second one: cases with congenital heart diseases (CHD) without pulmonary hypertension and the third group included healthy neonates. All participants were subjected to full history taking and full clinical examination. Diagnosis of congenital heart disease and pulmonary hypertension was made according to echocardiographic findings by pediatric cardiologist using echocardiography machine. Laboratory investigations included measurement of serum pentraxin 3, Routine CBC, CRP. RESULTS: This study found that the mean serum pentraxin 3 in PHT neonates was significantly higher than that of the control and CHD neonates (p ≤ 0.001, p = 0.02 respectively). Also, the mean Pentraxin3 of the CHD neonates was significantly higher than that of the control (p = 0.06). Also, the mean CRP of the PHT neonates was significantly higher than that of the control (p = 0.01). Regression analysis showed that Pentraxin3 was the main predictor of PAP (P = 0.01). CONCLUSION: Serum pentraxin 3 is significantly elevated in neonates with pulmonary hypertension, so measurement of pentraxin 3 levels in neonates may be valuable as a predictor for pulmonary hypertension in neonates.

Neurological Alterations in Type 1 Diabetes Mellitus Among Adolescents.

BACKGROUND: Diabetes mellitus (DM) is a group of chronic disorders of metabolism characterised by high blood glucose levels. There is an increased prevalence of Type 1 DM in children and adolescents with its adverse complications especially microvascular ones (retinopathy, nephropathy and neuropathy) that might cause multiple organ damage. AIM: To study the relation between DM and neurological affection. METHODS: Fifty-nine children with type I DM, divided randomly into 2 groups, aged 8-18 years old of both sexes were enrolled in this cross-sectional study. All children were subjected to full history taking, physical, neurological and systemic examination. RESULTS: There was an affection of motor power in both upper limbs as well as lower limbs. Also, we found that there was an affection of the superficial peripheral sensation affecting both upper and lower limbs. CONCLUSION: Neurological assessment of children with diabetes mellitus type I should be a routine to early discover these manifestations which can have a deteriorating effect on the child's health.