Clinical and genetic characterization of neuronal ceroid lipofuscinoses (NCLs) in 29 Iranian patients: identification of 11 novel mutations.
Samareh PanjeshahiParvaneh KarimzadehAbolfazl MovafaghFarzad AhmadabadiElham RahimianSahar AlijanpourMohammad MiryounesiPublished in: Human genetics (2023)
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.
Keyphrases
- copy number
- genome wide
- genome wide identification
- end stage renal disease
- dna methylation
- magnetic resonance imaging
- chronic kidney disease
- ejection fraction
- bioinformatics analysis
- transcription factor
- randomized controlled trial
- computed tomography
- peritoneal dialysis
- stem cells
- case report
- resting state
- functional connectivity
- brain injury
- magnetic resonance
- mild cognitive impairment
- early life
- cell therapy
- blood brain barrier
- subarachnoid hemorrhage