Abstract:

Objective

To investigate the clinical and genetic feasures of children with neurodegeneration with brain iron accumulation.

Methods

A retrospective analysis was conducted on the clinical manifestations and imaging data of six children with neurodegeneration with brain iron accumulation who were treated at the First Affiliated Hospital of Xinjiang Medical University from March 2021 to June 2024.Gene sequencing was performed on the children and their families using whole exome technology.

Results

Among the six pediatric patients, four were girls and two were boys, with ages ranging from 1 year and 7 months to 6 years old.All patients presented with comprehensive developmental delay clinically,and two patients showed significant developmental regression.Among them, one patient had myasthenia gravis (ocular muscle type).Gene sequencing showed that four children had WDR45 gene mutations,namely, c.519+1_519+3del c.381del, c.984C＞G, and c.400C＞T.After Sanger sequencing verification,all mutations were found to be de novo.Two cases had PLA2G6 gene mutations, with one case carrying both c.1547_1548dupCG (repeat mutation) and c.1799G＞A gene mutations, and the other case carrying c.1002dupA mutation.

Conclusion

Neurodegeneration with brain iron accumulation has clinical and genetic diversity.Whole exome gene sequencing, combined with medical history and MRI, can help with early diagnosis and guide treatment.The detection of new mutation sites broadens the spectrum of gene variation.

Key words: Neurodegeneration with brain iron accumulation, WDR45 gene, PLA2G6 gene, Genetic mutation, Whole exome sequencing, X-linked dominant inheritance