Abstract
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.
Highlights
Gene ABAT ABCD1 ACOX1 ADGRG1 AIMP1 ALDH3A2 AMACR APP ARSA ARSE ASPA ATP13A2 AUH BCAP31 BCS1L C19orf[12] CLCN2 COASY COX15 COX6B1 CP CSF1R CTC1 CYP27A1 DARS2 DCAF17 DDC DLD EIF2B1 EIF2B2 EIF2B3 EIF2B4 EIF2B5 ERCC6 ERCC8 ETHE1 FA2H FAM126A FASTKD2 FKTN FOLR1 FOXRED1 PC PEX1 PEX10 PEX12 PEX13 PEX16 PEX26 PEX5 PEX6 PHYH PLA2G6 PLP1 POLR3A POLR3B PSAP
Exons 5 12 those patients with leukoencephalopathies, we designed a custom probe library containing 118 genes reported to be associated with leukoencephalopathies (Table 1)
We summarized the clinical characteristics of the total 49 patients enrolled in this study and found 39 are male and 10 are female
Summary
Gene ABAT ABCD1 ACOX1 ADGRG1 AIMP1 ALDH3A2 AMACR APP ARSA ARSE ASPA ATP13A2 AUH BCAP31 BCS1L C19orf[12] CLCN2 COASY COX15 COX6B1 CP CSF1R CTC1 CYP27A1 DARS2 DCAF17 DDC DLD EIF2B1 EIF2B2 EIF2B3 EIF2B4 EIF2B5 ERCC6 ERCC8 ETHE1 FA2H FAM126A FASTKD2 FKTN FOLR1 FOXRED1 PC PEX1 PEX10 PEX12 PEX13 PEX16 PEX26 PEX5 PEX6 PHYH PLA2G6 PLP1 POLR3A POLR3B PSAP. Exons 5 12 those patients with leukoencephalopathies, we designed a custom probe library containing 118 genes reported to be associated with leukoencephalopathies (Table 1). We embarked on this study to assess the utility and effectiveness of targeted capture and MPS technology in 49 Chinese leukoencephalopathy patients. To our knowledge, this is the first study to use targeted gene capture and sequencing for leukoencephalopathies. 40.8% positive rate confirmed that the implementation of this method can accelerate diagnosis, reduce overall cost, and expand our knowledge of the genetic and clinical spectra of leukoencephalopathies This is the first study to use targeted gene capture and sequencing for leukoencephalopathies. 40.8% positive rate confirmed that the implementation of this method can accelerate diagnosis, reduce overall cost, and expand our knowledge of the genetic and clinical spectra of leukoencephalopathies
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