Objective: The current study was designed to investigate the genetic cause of atypical Parkinsonism is a multigenerational Pakistani family

Background: Hereditary Diffuse Leucoencephalopathy with axonal Spheroids (HDLs) is a neurodegenerative disease of white matter. Clinically diagnosis of HDLs is difficult because of overlapping symptoms with Parkinson’s disease and oftenly diagnosed as a typical Parkinsonism. Brain MRI shows white matter changes which is suggestive of leukodystrophy but is limited. HDLs is rare autosomal dominant neurodegenerative disease with no definitive diagnosis, however a range of mutation has been reported in CSF1R gene as the genetic cause of disease.   Genetic testing and elucidating the cause of pathophysiology will add in the diagnosis.

Method: Whole genome sequencing (WGS) was performed for patient II:4 and III:1. Bioinformatics analysis and narrowing down the data identified potential candidates’ genes. All the genes were verified with sanger re-sequencing.

Results: We investigated a family with several patients exhibiting clinical symptoms consistent with a typical Parkinsonism. The clinical features include difficulty in movements and dementia with slow progression. White matter changes were observed in the MRI suggestive of leukodystrophy. Whole genome sequencing identified a heterozygous c. 1237 G >A, mutation in exon 9 of CSF1R p. 413G>S.

Conclusion: Neurodegenerative diseases are multifactorial and difficult to diagnose clinically. Genetic investigations will add in identifying hot spots for the quicker diagnosis and thus add in the diagnostic panel.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-novel-g413s-mutation-in-the-csf1r-gene-causes-hereditary-diffuse-leucoencephalopathy-with-axonal-spheroids-clinically-overlapping-features-of-parkinsonism/