Key result
MYO5B or STX3 mutations cause microvillus inclusion disease by disrupting apical trafficking and inducing intractable diarrhea.
Why the study?
Microvillus inclusion disease is characterized by life-threatening watery diarrhoea in infancy with unclear molecular mechanisms involving apical trafficking defects.
Identifies STX3 and MYO5B mutations as genetic causes of microvillus inclusion disease, highlighting disrupted apical vesicle trafficking as the underlying mechanism.
May aid genetic diagnosis of MVID; leaves open broader variant spectrum and therapeutic translation.
Microvillus inclusion disease (MVID) is characterised by onset of intractable life-threatening watery diarrhoea during infancy. Transmission electron microscopy demonstrates shortening or absence of apical microvilli, pathognomonic microvillus inclusions in mature enterocytes and subapical accumulation of periodic acid-Schiff-positive granules or vesicles confirming diagnosis. Mutations in MYO5B have been found to cause MVID. In two patients with MVID, whole-exome sequencing of DNA revealed homozygous truncating mutations in STX3. Mutations in these genes disrupt trafficking between apical cargo vesicles and the apical plasma membrane. Thus, disturbed delivery of certain brush border membrane proteins is a common defect in MVID.
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Vogel et al. (2016) conducted a review in Microvillus inclusion disease (MVID). Microvillus inclusion disease is a severe congenital enteropathy caused by mutations in MYO5B or STX3 that disrupt apical trafficking and cause intractable watery diarrhea.
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