An Overview and Online Registry of Microvillus Inclusion Disease Patients and theirMYO5BMutations

Abstract

Microvillus inclusion disease (MVID) is one of the most severe congenital intestinal disorders and is characterized by neonatal secretory diarrhea and the inability to absorb nutrients from the intestinal lumen. MVID is associated with patient-, family-, and ancestry-unique mutations in the MYO5B gene, encoding the actin-based motor protein myosin Vb. Here, we review the MYO5B gene and all currently known MYO5B mutations and for the first time methodologically categorize these with regard to functional protein domains and recurrence in MYO7A associated with Usher syndrome and other myosins. We also review animal models for MVID and the latest data on functional studies related to the myosin Vb protein. To congregate existing and future information on MVID geno-/phenotypes and facilitate its quick and easy sharing among clinicians and researchers, we have constructed an online MOLGENIS-based international patient registry (www.MVID-central.org). This easily accessible database currently contains detailed information of 137 MVID patients together with reported clinical/phenotypic details and 41 unique MYO5B mutations, of which several unpublished. The future expansion and prospective nature of this registry is expected to improve disease diagnosis, prognosis, and genetic counseling.

Disrupted apical exocytosis of cargo vesicles causes enteropathy in FHL5 patients with Munc18-2 mutations

“…13,14), recently identified as aberrant Rab11-Rab8-positive recycling compartments (17). Genetic analysis revealed that mutations in the MYOB5 or STX3 genes are causative for MVID (18)(19)(20)(21).…”

Myosin Vb uncoupling from RAB8A and RAB11A elicits microvillus inclusion disease

“…It should be noted the predominant splice variant of MYO5B in enterocytes lacks exon D (17). Mutations that disrupt the function of the motor, lever arm, calmodulin binding, or RAB binding or induce premature termination before the tail domain can lead to MVID (1,4,6,9).…”

“…No studies until now have identified conclusively the origin or nature of these structures (22,23). The accumulation of PAS-positive "granules" also occurs at higher frequency in samples from patients with MVID than in the enterocytes of normal duodenum (9). MVID is uniformly fatal and no current pharmacotherapy exists, but it can be treated with total parenteral nutrition or an intestinal transplant (24).…”

The zebrafish goosepimples/myosin Vb mutant exhibits cellular attributes of human microvillus inclusion disease

“…An international patient registry reports 41 unique myosin Vb mutations thought to be associated with MVID (van der Velde et al, 2013). Myosin Vb is an actin based molecular motor.…”