The use of targeted genomic capture and massively parallel sequencing in diagnosis of Chinese Leukoencephalopathies

Leukoencephalopathies are diseases with high clinical heterogeneity. In clinical work, it's difficult for doctors to make a definite etiological diagnosis. Here, we designed a custom probe library which contains the known pathogenic genes reported to be associated with Leukoencephalopathies, and performed targeted gene capture and massively parallel sequencing (MPS) among 49 Chinese patients who has white matter damage as the main imaging changes, and made the validation by Sanger sequencing for the probands' parents. As result, a total of 40.8% (20/49) of the patients identified pathogenic mutations, including four associated with metachromatic leukodystrophy, three associated with vanishing white matter leukoencephalopathy, three associated with mitochondrial complex I deficiency, one associated with Globoid cell leukodystrophy (or Krabbe diseases), three associated with megalencephalic leukoencephalopathy with subcortical cysts, two associated with Pelizaeus-Merzbacher disease, two associated with X-linked adrenoleukodystrophy, one associated with Zellweger syndrome and one associated with Alexander disease. Targeted capture and MPS enables to identify mutations of all classes causing leukoencephalopathy. Our study combines targeted capture and MPS technology with clinical and genetic diagnosis and highlights its usefulness for rapid and comprehensive genetic testing in the clinical setting. This method will also expand our knowledge of the genetic and clinical spectra of leukoencephalopathy.