Exome sequencing for mucolipidosis III: Detection of a novel GNPTAB gene mutation in a patient with a very mild phenotype

• Main Authors: F. Sperb-Ludwig, T. Alegra, R.V. Velho, N. Ludwig, C.A. Kim, F. Kok, J.P. Kitajima, E. van Meel, S. Kornfeld, M.G. Burin, I.V.D. Schwartz
• Format: Article
• Language: English
• Published: Elsevier 2015-03-01
• Series: Molecular Genetics and Metabolism Reports
• Subjects: Mucolipidosis II/III alpha/beta; Whole exome sequencing; Molecular diagnosis
• Online Access: http://www.sciencedirect.com/science/article/pii/S2214426914000809
• ISSN: 2214-4269

Mucolipidosis II and III alpha/beta (ML II/III alpha/beta) are rare autosomal recessive lysosomal storage diseases that are caused by a deficiency of UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase, the enzyme responsible for the synthesis of the mannose 6-phosphate targeting signal on lysosomal hydrolases. A Brazilian patient suspected of having a very mild ML III was investigated using whole next-generation sequencing (NGS). Two mutations in the GNPTAB gene were detected and confirmed to be in trans status by parental analysis: c.1208T>C (p.Ile403Thr), previously reported as being pathogenic, and the novel mutation c.1723G>A (p.Gly575Arg). This study demonstrates the effectiveness of using whole NGS for the molecular diagnosis of very mild ML III alpha/beta patients.