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1.
Neurogenetics ; 24(4): 279-289, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37597066

RESUMO

Leukodystrophies (LDs) are a heterogeneous group of progressive neurological disorders and characterized by primary involvement of white matter of the central nervous system (CNS). This is the first report of the Iranian LD Registry database to describe the clinical, radiological, and genomic data of Persian patients with leukodystrophies. From 2016 to 2019, patients suspicious of LDs were examined followed by a brain magnetic resonance imaging (MRI). A single gene testing or whole-exome sequencing (WES) was used depending on the neuroradiologic phenotypes. In a few cases, the diagnosis was made by metabolic studies. Based on the MRI pattern, diagnosed patients were divided into cohorts A (hypomyelinating LDs) versus cohort B (Other LDs). The most recent LD classification was utilized for classification of diagnosed patients. For novel variants, in silico analyses were performed to verify their pathogenicity. Out of 680 registered patients, 342 completed the diagnostic evaluations. In total, 245 patients met a diagnosis which in turn 24.5% were categorized in cohort A and the remaining in cohort B. Genetic tests revealed causal variants in 228 patients consisting of 213 variants in 110 genes with 78 novel variants. WES and single gene testing identified a causal variant in 65.5% and 34.5% cases, respectively. The total diagnostic rate of WES was 60.7%. Lysosomal disorders (27.3%; GM2-gangliosidosis-9.8%, MLD-6.1%, KD-4.5%), amino and organic acid disorders (17.15%; Canavan disease-4.5%, L-2-HGA-3.6%), mitochondrial leukodystrophies (12.6%), ion and water homeostasis disorders (7.3%; MLC-4.5%), peroxisomal disorders (6.5%; X-ALD-3.6%), and myelin protein disorders (3.6%; PMLD-3.6%) were the most commonly diagnosed disorders. Thirty-seven percent of cases had a pathogenic variant in nine genes (ARSA, HEXA, ASPA, MLC1, GALC, GJC2, ABCD1, L2HGDH, GCDH). This study highlights the most common types as well as the genetic heterogeneity of LDs in Iranian children.


Assuntos
Doenças Desmielinizantes , Doenças Neurodegenerativas , Humanos , Criança , Irã (Geográfico) , Heterogeneidade Genética , Imageamento por Ressonância Magnética , Encéfalo , Oxirredutases do Álcool
2.
Neuropediatrics ; 50(2): 130-134, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30791064

RESUMO

Leukodystrophies are heterogeneous group of genetic white matter disorders with a wide range of neurologic and systemic manifestations. Defects in genes encoding aminoacyl tRNA (transfer ribonucleic acid) synthetase enzymes (aaRSs) are recently identified as the etiology of some leukodystrophies. Herein, we described two unrelated children referred to Children's Medical Center, Tehran, Iran, with developmental delay, nystagmus, seizures, psuedo-bulbar palsy and dystonia. Whole exome sequencing (WES) in both patients identified a homozygous (c.2T > C) variant in exon one of RARS gene, encoding cytoplasmic arginyl-tRNA synthetase. Our finding was confirmed by segregation analysis. In silico analyses of the c.2T > C variant showed its possible pathogenic role due to the absence of the start codon. Severe hypomyelination was the common neuroimaging finding of both cases. Spinal cord involvement was found in one of our patients which was not previously reported in studies. We, therefore, showed that RARS-related hypomyelination might affect spinal cord.


Assuntos
Aminoacil-tRNA Sintetases/genética , Variação Genética/genética , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/diagnóstico por imagem , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Medula Espinal/diagnóstico por imagem , Aminoacil-tRNA Sintetases/química , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estrutura Secundária de Proteína
4.
Clin Case Rep ; 11(4): e7253, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37102104

RESUMO

Acknowledging the risk factors of mortality and morbidity of each disease is effective for its final outcome. Recognizing these cases can have the value of preventing the occurrence of unfortunate events, such as not recommending the use diclofenac in an influenza epidemic.

5.
Iran J Child Neurol ; 17(2): 19-29, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37091468

RESUMO

Objectives: Mutations in TSC1 or TSC2 genes have been proposed as the main causative factors responsible for developing Tuberous Sclerosis Complex (TSC). Given the effect of these two genes on the mTOR pathway, rapamycin has emerged as a novel therapeutic agent. The present study evaluated the effectiveness and safety of rapamycin on the multiple manifestations of TSC. Materials & Methods: Twenty-three eligible children were enrolled in the present cross-sectional study. They were prescribed rapamycin 1mg tablet twice daily for the first two weeks of treatment and then once daily for at least one year. Periodic evaluations through follow-up visits were performed. Besides, growth and developmental statuses were evaluated. All data, including the number and size of brain tuberomas, size of renal angiomyolipomas, and skin lesions, were gathered and recorded, and then analyzed. Results: During the study period, the mean number of epileptic episodes significantly reduced (p<0.0001), and nine cases were seizure-free at the final visit. The mean number of brain tuberomas decreased from 19.3±11.0 at the initial visit to 11.1±5.6 and 8.2±3.2 in the subsequent visits (p<0.001). The mean size of brain tuberomas similarly decreased from 17.9±18.5 cm at enrollment to 13.7±5.1 cm and 6.9±5.1 cm in the second and third visits, respectively (p=0.029). The mean size of renal angiomyolipomas significantly decreased (p<0.001). A significant trend toward a decrease in the number of skin lesions was observed (p<0.0001). No relationship was observed between the effects of rapamycin and the patient's age or sex (p>0.05). Changes in patients' growth and developmental features were not statistically significant through subsequent visits (p=0.507). Conclusion: This study revealed the effectiveness and safety of rapamycin on TSC among our patients.

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