Mutations in Myosin 5B in Children With Early-onset Cholestasis.
Journal
Journal of pediatric gastroenterology and nutrition
ISSN: 1536-4801
Titre abrégé: J Pediatr Gastroenterol Nutr
Pays: United States
ID NLM: 8211545
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
pubmed:
19
4
2020
medline:
22
6
2021
entrez:
19
4
2020
Statut:
ppublish
Résumé
Mutations in Myosin 5B (MYO5B) are known to be associated with microvillous inclusion disease (MVID) a genetic cause of neonatal intractable diarrhoea. More recently, they have been reported in children with cholestasis but without typical gastrointestinal symptoms of MVID. We describe our series of children with cholestasis and mutations in MYO5B. Clinical, laboratory, and histological data were collected from patients with cholestasis and pathogenic mutations in MYO5B, found by next generation sequencing (NGS) but with minimal gastrointestinal disease. Six patients (3 boys) were identified. Median age at presentation was 19 months (range, 3-92). Presenting features were jaundice, pale stools, pruritus, and failure to thrive. Patients 5 and 6 had intractable diarrhoea until the age of 3 and 7 years, respectively, but currently are on full enteral diet with no intestinal symptoms. Median values for serum total bilirubin were 55 μmol/L (2-500), alanine aminotransferase 73I IU/L (32-114), γ-glutamyltransferase 7 IU/L (7-10), and serum bile acids 134 μmol/L (18-274). Three patients underwent 1 or more types of biliary diversion for symptom control. Median follow-up was 5 years (2-22). At most recent follow-up, they all reported pruritus while on antipruritics. Patient 1 had a liver transplant. We identified 6 patients, with mutations in MYO5B, early-onset cholestasis and pruritus, with variable response to biliary diversion without typical MVID.
Identifiants
pubmed: 32304554
doi: 10.1097/MPG.0000000000002740
pii: 00005176-202008000-00011
doi:
Substances chimiques
MYO5B protein, human
0
Myosin Type V
EC 3.6.1.-
Myosin Heavy Chains
EC 3.6.4.1
Myosins
EC 3.6.4.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
184-188Références
Schlegel C, Weis VG, Knowles BC, et al. Apical membrane alterations in non-intestinal organs in microvillus inclusion disease. Dig Dis Sci 2018; 63:356–365.
Golachowska MR, van Dael CM, Keuning H, et al. MYO5B mutations in patients with microvillus inclusion disease presenting with transient renal Fanconi syndrome. J Pediatr Gastroenterol Nutr 2012; 54:491–498.
Thoeni CE, Vogel GF, Tancevski I, et al. Microvillus inclusion disease: loss of Myosin vb disrupts intracellular traffic and cell polarity. Traffic 2014; 15:22–42.
Weis VG, Knowles BC, Choi E, et al. Loss of MYO5B in mice recapitulates Microvillus Inclusion Disease and reveals an apical trafficking pathway distinct to neonatal duodenum. Cell Mol Gastroenterol Hepatol 2016; 2:131–157.
Halac U, Lacaille F, Joly F, et al. Microvillous inclusion disease: how to improve the prognosis of a severe congenital enterocyte disorder. J Pediatr Gastroenterol Nutr 2011; 52:460–465.
Qiu YL, Gong JY, Feng JY, et al. Defects in myosin VB are associated with a spectrum of previously undiagnosed low gamma-glutamyltransferase cholestasis. Hepatology 2017; 65:1655–1669.
Girard M, Lacaille F, Verkarre V, et al. MYO5B and bile salt export pump contribute to cholestatic liver disorder in microvillous inclusion disease. Hepatology 2014; 60:301–310.
Lam P, Xu S, Soroka CJ, et al. A C-terminal tyrosine-based motif in the bile salt export pump directs clathrin-dependent endocytosis. Hepatology 2012; 55:1901–1911.
Gonzales E, Taylor SA, Davit-Spraul A, et al. MYO5B mutations cause cholestasis with normal serum gamma-glutamyl transferase activity in children without microvillous inclusion disease. Hepatology 2017; 65:164–173.
Wakabayashi Y, Dutt P, Lippincott-Schwartz J, et al. Rab11a and myosin Vb are required for bile canalicular formation in WIF-B9 cells. Proc Natl Acad Sci U S A 2005; 102:15087–15092.
Croft NM, Howatson AG, Ling SC, et al. Microvillous inclusion disease: an evolving condition. J Pediatr Gastroenterol Nutr 2000; 31:185–189.
Bull LN, van Eijk MJ, Pawlikowska L, et al. A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Nat Genet 1998; 18:219–224.
Strautnieks SS, Bull LN, Knisely AS, et al. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet 1998; 20:233–238.
Beuers U, Trauner M, Jansen P, et al. New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond. J Hepatol 2015; 62:S25–S37.
Shneider BL, Spino C, Kamath BM, et al. Placebo-controlled randomized trial of an intestinal bile salt transport inhibitor for pruritus in Alagille syndrome. Hepatol Commun 2018; 2:1184–1198.
Chen CP, Chiang MC, Wang TH, et al. Microvillus inclusion disease: prenatal ultrasound findings, molecular diagnosis and genetic counseling of congenital diarrhea. Taiwan J Obstet Gynecol 2010; 49:487–494.
Erickson RP, Larson-Thome K, Valenzuela RK, et al. Navajo microvillous inclusion disease is due to a mutation in MYO5B. Am J Med Genet A 2008; 146A:3117–3119.
Perry A, Bensallah H, Martinez-Vinson C, et al. Microvillous atrophy: atypical presentations. J Pediatr Gastroenterol Nutr 2014; 59:779–785.
Ruemmele FM, Muller T, Schiefermeier N, et al. Loss-of-function of MYO5B is the main cause of microvillus inclusion disease: 15 novel mutations and a CaCo-2 RNAi cell model. Hum Mutat 2010; 31:544–551.
Szperl AM, Golachowska MR, Bruinenberg M, et al. Functional characterization of mutations in the myosin Vb gene associated with microvillus inclusion disease. J Pediatr Gastroenterol Nutr 2011; 52:307–313.