Using whole-exome sequencing to investigate the genetic bases of lysosomal storage diseases of unknown etiology

Nan Wang, Yeting Zhang, Erika Gedvilaite, Jui Wan Loh, Timothy Lin, Xiuping Liu, Chang Gong Liu, Dibyendu Kumar, Robert Donnelly, Kimiyo Raymond, Edward H. Schuchman, David E. Sleat, Peter Lobel, Jinchuan Xing

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Lysosomes are membrane-bound, acidic eukaryotic cellular organelles that play important roles in the degradation of macromolecules. Mutations that cause the loss of lysosomal protein function can lead to a group of disorders categorized as the lysosomal storage diseases (LSDs). Suspicion of LSD is frequently based on clinical and pathologic findings, but in some cases, the underlying genetic and biochemical defects remain unknown. Here, we performed whole-exome sequencing (WES) on 14 suspected LSD cases to evaluate the feasibility of using WES for identifying causal mutations. By examining 2,157 candidate genes potentially associated with lysosomal function, we identified eight variants in five genes as candidate disease-causing variants in four individuals. These included both known and novel mutations. Variants were corroborated by targeted sequencing and, when possible, functional assays. In addition, we identified nonsense mutations in two individuals in genes that are not known to have lysosomal function. However, mutations in these genes could have resulted in phenotypes that were diagnosed as LSDs. This study demonstrates that WES can be used to identify causal mutations in suspected LSD cases. We also demonstrate cases where a confounding clinical phenotype may potentially reflect more than one lysosomal protein defect.

Original languageEnglish
Pages (from-to)1491-1499
Number of pages9
JournalHuman Mutation
Issue number11
StatePublished - Nov 2017


  • disease-causing variants identification
  • lysosomal storage diseases
  • metabolic disorders
  • whole-exome sequencing


Dive into the research topics of 'Using whole-exome sequencing to investigate the genetic bases of lysosomal storage diseases of unknown etiology'. Together they form a unique fingerprint.

Cite this