👤 Parvaneh Karimzadeh

Mutations in the branched-chain keto-acid dehydrogenase kinase gene (BCKDK), leading to low plasma branched-chain amino acids (BCAAs) levels, have been reported as a contributor to comorbid intellectual disability, autism, epilepsy, and neurodevelopmental delay (NDD). Due to the rarity of knowledge about these mutations, the current case series aims to introduce four confirmed cases. This case series study analyzed children from a neurometabolic clinic. Social and adaptive functions were assessed using the vineland social maturity scale (VSMS). Whole exome sequencing (WES) identified genetic variants filtered using population databases. Candidate variants were confirmed through Sanger sequencing and interpreted based on ACMG guidelines. Four children of unrelated consanguineous families suffering from global NDD and autism were referred to our center. Neuroimaging assessments revealed negligible findings; thus, metabolic tests were sent, in which BCAAs were lower than normal limits. Therefore, genetic testing was done, and genetic variants compatible with BCKDK deficiency were detected. By initiating a BCAAs-rich regimen, the patients had significant improvements in psychomotor and speech development. The diagnosis of BCKDK deficiency should be suspected in patients with NDD and autism, and BCAA supplementation should be initiated as soon as diagnosis confirmation to prevent irreversible brain damage. The results emphasize that early diagnosis and dietary intervention by regulating plasma BCAA levels lead to the prevention of irreversible neurodevelopmental implications. Show less

Neuronal ceroid lipofuscinoses (NCLs) are neurodegenerative lysosomal storage diseases which are considered among the most frequent causes of dementia in childhood worldwide This study aimed to identify the gene variants, molecular etiologies, and clinical features in 23 unrelated Iranian families with NCL. In total, 29 patients with neuronal ceroid lipofuscinoses (NCLs), diagnosed based on clinical manifestations, MRI neuroimaging, and electroencephalography (EEG), were recruited for this study. Through whole-exome sequencing (WES), functional prediction, Sanger sequencing, and segregation analysis, we found that 12 patients (41.3%) with mutations in the CLN6 gene, 7 patients (24%) with the TPP1 (CLN2) gene variants, and 4 patients (13.7%) with mutations in the MFSD8 (CLN7) gene. Also, mutations in each of the CLN3 and CLN5 genes were detected in 2 cases and mutations of each PPT1 (CLN1) and CLN8 gene were observed in only 1 separate patient. We identified 18 different mutations, 11 (61%) of which are novel, never have been reported before, and the others have been previously described. The gene variants identified in this study expand the number of published clinical cases and the variant frequency spectrum of the neuronal ceroid lipofuscinoses (NCLs) genes; moreover, the identification of these variants supplies foundational clues for future NCL diagnosis and therapy. Show less

Systemic lupus erythematosus (SLE) is an autoimmune disease with multifactorial etiology. Several studies show that genetic factors have an important part in the incidence of SLE. The C1QTNF4 gene is involved in the regulation of the inflammatory pathways by pro-inflammatory function. In the present study, we have evaluated the association between C1QTNF4 gene p.His198Gln mutation and risk of SLE. Forty SLE patients and 40 control subjects were recruited in this case-control study. Genotyping of C1QTNF4 p.His198Gln mutation was performed using real-time polymerase chain reaction high resolution melting method. We found a significant association between this mutation (GG + GC) with the risk of SLE (odds ratio = 6.33, 95% CI = 1.28-31.11). Furthermore, we observed that in the patient group, this mutation leads to early-onset SLE (19.7 ± 4.34 years for mutation carriers compared to 27.7 ± 11.4 years for wild type carriers; P = .003). Our results suggest that this mutation (p.His198Gln) potentially has an important role in SLE risk in the Iranian population. Show less

We aimed to perform genetic testing and clinical data of patients with Congenital Myasthenic Syndrome, a rare disorder caused by mutations in genes encoding molecules expressed in the neuromuscular junction and constitutes fatigable muscle weakness. Sixteen patients were screened in Taban Clinic, Tehran, Iran from 2014 to 2015 for the hot spot mutations in known CMSs genes ( Most patients represented the criteria of Congenital Myasthenic Syndrome in view of early ptosis, motor delay, normal mental development, easy fatigability, decrement in repetitive nerve stimulation test of EMG-NCV and a negative result for antibody against of acetylcholine receptor. No variations were found in the mutational analysis of the The common founder mutations of involved genes in CMSs could be very rare among ethnic Iranian. Screening of the entire genes would be efficient to distinguish the specific mutations in specific ethnicity. Show less