Mutations in CSPP1, TMEM67, PLP1, and GAN associated with pediatric neurological disorders in Iran

Background & Objective: Neurological disorders significantly impact patients' mental, personality, and movement functions, with a rising prevalence globally, especially in low-income and middle- income countries. This study aims to evaluate gene mutations in pediatric neurological disorders patients to contribute to our understanding of these disorders' genetic basis. Methods: In the current survey, all patients with maternal signs of neurological disorders who were referred to the neurology department during 2023 to 2024 were evaluated. DNA samples from patients were enriched using the Agilent SureSelect Human All Exon Kit V6, and subsequent sequencing took place on an Illumina HiSeq 4000 platform based on the manufacturer's procedures. Results: In the current cross-sectional study, 13 patients with maternal neurological disorders including 6 males (46%) and 7 females (54%) were evaluated. Our results identified inherited neurological disorders, including Joubert syndrome, Pelizaeus-Merzbacher disease, and giant axonal neuropathy-1. Our data identified a novel missense mutation in exon 8 of PLP1 gene (NM_001128834.3: c.772A>C; p.Met258Leu) with X-linked recessive inheritance in a patient with Pelizaeus-Merzbacher disease. Gene variants, including CSPP1 frameshift mutation in exon 20 (NM_001382391.1: c.2259_2260delAA; p.Glu755GlyfsTer30), and autosomal recessive homozygous TMEM67 mutation in exon 8 (NM_153704.6: c.725A>G; p.Asn242Ser) were detected in patients with Joubert syndrome. Finally, in a patient with giant axonal neuropathy-1, a homozygous GAN mutation (NM_022041.4: c.1177T>C; p.Cys393Arg) was detected. Conclusion: Our findings can be useful in understanding the pathophysiology of neurological disorders. Also, this study indicated the importance of genetic analysis in utilizing the treatment strategy in patients with neurological disorders.