Apical Membrane Alterations in Non-intestinal Organs in Microvillus Inclusion Disease.
Dig Dis Sci
; 63(2): 356-365, 2018 02.
Article
en En
| MEDLINE
| ID: mdl-29218485
ABSTRACT
OBJECTIVES:
Microvillus inclusion disease (MVID) is a severe form of neonatal diarrhea, caused mainly by mutations in MYO5B. Inactivating mutations in MYO5B causes depolarization of enterocytes in the small intestine, which gives rise to chronic, unremitting secretory diarrhea. While the pathology of the small intestine in MVID patients is well described, little is known about extraintestinal effects of MYO5B mutation.METHODS:
We examined stomach, liver, pancreas, colon, and kidney in Navajo MVID patients, who share a single homozygous MYO5B-P660L (1979C>T p.Pro660Leu, exon 16). Sections were stained for markers of the apical membrane to assess polarized trafficking.RESULTS:
Navajo MVID patients showed notable changes in H/K-ATPase-containing tubulovesicle structure in the stomach parietal cells. Colonic mucosa was morphologically normal, but did show losses in apical ezrin and Syntaxin 3. Hepatocytes in the MVID patients displayed aberrant canalicular expression of the essential transporters MRP2 and BSEP. The pancreas showed small fragmented islets and a decrease in apical ezrin in pancreatic ducts. Kidney showed normal primary cilia.CONCLUSIONS:
These findings indicate that the effects of the P660L mutation in MYO5B in Navajo MVID patients are not limited to the small intestine, but that certain tissues may be able to compensate functionally for alterations in apical trafficking.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_diarrhea
Asunto principal:
Membrana Celular
/
Síndromes de Malabsorción
/
Microvellosidades
/
Mucolipidosis
Límite:
Child
/
Female
/
Humans
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Infant
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Male
/
Newborn
Idioma:
En
Revista:
Dig Dis Sci
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos