RESUMO
INTRODUCTION: Mutations in GDAP1 (Ganglioside-induced differentiation-associated protein 1) gene are linked to Charcot-Marie-Tooth disease (CMT), a Heterogenous group of disorders with multiple phenotypes, characterized by peripheral nerve dysfunction that can lead to vocal cord paralysis and diaphragmatic dysfunction. MAIN BODY: All three affected children of this chosen family have manifested the same clinical symptoms with progressive weakness, mild sensory impairment, and absent tendon reflexes in their early years. Electrodiagnostic analysis displayed an axonal type of neuropathy in affected patients. Sequencing of the GDAP1 gene was requested for all members of the family. Diagnostic assessments included pulmonary and vocal cord function tests, as well as phrenic and peripheral nerve conduction studies. Pathogenicity of GDAP1 variant p.Pro419Leu with axonal CMT2 and autosomal recessive inheritance was confirmed via in silico analysis. Patients with GDAP1 mutations showed dysphonia, speech difficulties, and the characteristic symptoms of CMT. The severity of symptoms correlated with the presence of a type of GDAP1 mutation. Patients with normal vocal cords and pulmonary function exhibited milder symptoms compared to those with GDAP1 mutations. Our study provides clinical insights into the phenotypic effects of GDAP1 mutations in CMT patients. The findings highlight the adverse clinical course and severe disability associated with GDAP1 mutations, including weak limb and laryngeal muscles. CONCLUSION: Patients with GDAP1 mutations and autosomal recessive neuropathy present with dysphonia and require interventions such as surgery, braces, physical therapy, and exercise. Early diagnosis and comprehensive clinical evaluations are crucial for managing CMT patients with GDAP1 mutations.
RESUMO
Relative ecotoxicity of approved neonicotinoids (i.e. imidacloprid, clothianidin, acetamiprid, thiacloprid, thiamethoxam and dinotefuran) and diamides (i.e. chlorantraniliprole, cyantraniliprole and flubendiamide) was examined on population growth parameters of Zygogramma bicolorata Pallister on parthenium under laboratory conditions at 27 ± 1 °C, 65 ± 5% relative humidity and 10 L : 14D photoperiod. The dose of all tested insecticides in the bioassay procedure was within a minimum range of their recommended field rate. In acute toxicity trial, imidacloprid caused highest rate of mortality in treated adults of Z. bicolorata, however, it was lowest in flubendiamide treatment followed by cyantraniliprole and chlorantraniliprole. Further, based on toxicity coefficient (E) value in acute toxicity trial, all were classified as harmful (H) and diamides were classified as moderately harmful (MH) as per IOBC classification. Moreover, chronic toxicity trials were carried out through life table response experiments (LTREs) in the F1 progeny of acute toxicity experienced group. Prolonged development with the highest mortality was evident in as compared to diamides. Furthermore, population growth parameters i.e. potential fecundity (Pf), natality rate (mx), intrinsic rate of increase (rm), net reproductive rate (R0) and finite rate of increase (λ) was greatly reduced in Z. bicolorata treated with neonicotinoids as compared with diamides. However, mean generation time (Tc), corrected generation time (τ) and the doubling time (DT) was prolonged in neonicotinoids followed by diamides. Furthermore, proportion of females was greatly reduced (0.43-0.48 females) in neonicotinoids as comparison to diamides (0.53-0.55 females) and control (0.67 females). On the basis of ecotoxicity trials, the tested neonicotinoids were highly toxic to Z. bicolorata than diamides. Therefore, diamide insecticides could be used with Z. bicolorata, however, for validation experimentation need to be done under natural field conditions.
