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MYO5B, STX3, and STXBP2 mutations reveal a common disease mechanism that unifies a subset of congenital diarrheal disorders: A mutation update

Dhekne, H. S., Pylypenko, O., Overeem, A. W., Ferreira, R. J., van der Velde, K. J., Rings, E. H. H. M., Posovszky, C., Swertz, M. A., Houdusse, A. & van IJzendoorn, S. C. D., Mar-2018, In : Human Mutation. 39, 3, p. 333-344 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

Microvillus inclusion disease (MVID) is a rare but fatal autosomal recessive congenital diarrheal disorder caused by MYO5B mutations. In 2013, we launched an open-access registry for MVID patients and their MYO5B mutations (www.mvid-central.org). Since then, additional unique MYO5B mutations have been identified in MVID patients, but also in non-MVID patients. Animal models have been generated that formally prove the causality between MYO5B and MVID. Importantly, mutations in two other genes, STXBP2 and STX3, have since been associated with variants of MVID, shedding new light on the pathogenesis of this congenital diarrheal disorder. Here, we review these additional genes and their mutations. Furthermore, we discuss recent data from cell studies that indicate that the three genes are functionally linked and, therefore, may constitute a common disease mechanism that unifies a subset of phenotypically linked congenital diarrheal disorders. We present new data based on patient material to support this. To congregate existing and future information on MVID geno-/phenotypes, we have updated and expanded the MVID registry to include all currently known MVID-associated gene mutations, their demonstrated or predicted functional consequences, and associated clinical information.

Original languageEnglish
Pages (from-to)333-344
Number of pages12
JournalHuman Mutation
Volume39
Issue number3
Publication statusPublished - Mar-2018

    Keywords

  • congenital diarrheal diseases, enteropathy, microvillus inclusion disease, munc18-2, MYO5B, myosin VB, STX3, STXBP2, syntaxin-3, MICROVILLUS INCLUSION DISEASE, LYMPHOHISTIOCYTOSIS TYPE 5, EPITHELIAL-CELL POLARITY, SYNTAXIN 3, MYOSIN VB, MEMBRANE TRAFFICKING, INTESTINAL-CELLS, EXOCYTOSIS, DEFECTS, ATROPHY

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