关键词: 脑组织铁沉积神经变性病, 全外显子测序, 临床表型, 儿童

Abstract:

Objective The aim of this study was to explore the clinical and genetic characteristics of 7 pediatric patients with neurodegeneration with brain iron accumulation (NBIA). Methods Genetic mutation analysis was conducted on patients suspected of having NBIA using whole exome sequencing (WES), followed by Sanger sequencing for positive cases. A retrospective analysis of the patients' clinical data was performed alongside a literature review. Results Seven patients, comprising five boys and two girls with an average age of 5.4±3.8 years, presented to the hospital primarily due to motor developmental delay. The main clinical manifestations included intellectual disability, gait disorders, abnormal posture, delayed or regressed psychomotor development, muscle weakness, cerebellar ataxia, and retinitis pigmentosa. WES identified pathogenic mutations in NBIA-related genes in all 7 patients, specifically PANK2 in one case, FA2H in one case, and PLA2G6 in five cases. Patients with PLA2G6 variations exhibited early onset, developmental delay, muscle weakness, low signal iron deposition in the pallidus, and cerebellar atrophy. The patient with a PANK2 gene mutation showed gait and postural abnormalities, while the patient with an FA2H mutation presented with language delay, gait abnormalities, and dysmyotonia. Conclusion There is significant heterogeneity in the clinical phenotype of NBIA patients, with neurological abnormalities being the predominant feature. Two previously unreported variants were identified, broadening the spectrum of genetic variations in NBIA disease.

Key words: neurodegeneration with brain iron accumulation, WES, clinical manifestation, child