The Experts below are selected from a list of 192 Experts worldwide ranked by ideXlab platform
Emmanuel Jacquemin - One of the best experts on this subject based on the ideXlab platform.
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myo5b mutations cause cholestasis with normal serum gamma glutamyl transferase activity in children without Microvillous Inclusion Disease
Hepatology, 2017Co-Authors: Emmanuel Gonzales, Sarah A Taylor, Anne Davitspraul, Alice Thebaut, Nadege Thomassin, Catherine Guettier, Peter F Whitington, Emmanuel JacqueminAbstract:Some patients with microvillus Inclusion Disease due to myosin 5B (MYO5B) mutations may develop cholestasis characterized by a progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity. So far MYO5B deficiency has not been reported in patients with such a cholestasis phenotype in the absence of intestinal Disease. Using a new-generation sequencing approach, we identified MYO5B mutations in five patients with progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity without intestinal Disease. Conclusion: These data show that MYO5B deficiency may lead to isolated cholestasis and that MYO5B should be considered as an additional progressive familial intrahepatic cholestasis gene. (Hepatology 2017;65:164-173).
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MYO5B mutations cause cholestasis with normal serum gamma‐glutamyl transferase activity in children without Microvillous Inclusion Disease
Hepatology (Baltimore Md.), 2016Co-Authors: Emmanuel Gonzales, Sarah A Taylor, Alice Thebaut, Nadege Thomassin, Catherine Guettier, Peter F Whitington, Anne Davit-spraul, Emmanuel JacqueminAbstract:Some patients with microvillus Inclusion Disease due to myosin 5B (MYO5B) mutations may develop cholestasis characterized by a progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity. So far MYO5B deficiency has not been reported in patients with such a cholestasis phenotype in the absence of intestinal Disease. Using a new-generation sequencing approach, we identified MYO5B mutations in five patients with progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity without intestinal Disease. Conclusion: These data show that MYO5B deficiency may lead to isolated cholestasis and that MYO5B should be considered as an additional progressive familial intrahepatic cholestasis gene. (Hepatology 2017;65:164-173).
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MYO5B and BSEP contribute to cholestatic liver disorder in Microvillous Inclusion Disease.
Hepatology, 2013Co-Authors: Muriel Girard, Florence Lacaille, Virginie Verkarre, Raphael Mategot, Gerard Feldmann, Alain Grodet, Frédérique Sauvat, Sabine Irtan, Anne Davit-spraul, Emmanuel JacqueminAbstract:: Background and aims: Microvillous Inclusion Disease (MVID) is a congenital disorder of the enterocyte related to mutations in the MYO5B gene, leading to intractable diarrhea indicating intestinal transplantation (ITx). Among our cohort of 28 MVID patients, 8 developed a cholestatic liver Disease akin to progressive familial intrahepatic cholestasis (PFIC). Our aim was to investigate the mechanisms by which MYO5B mutations affect hepatic biliary function and lead to cholestasis in MVID patients. Methods: Clinical, biological features and outcome were reviewed. Pre-transplant liver biopsies were analyzed by immunostaining and electron microscopy. Results: Cholestasis occurred before (n=5) or after (n=3) ITx and was characterized by intermittent jaundice, intractable pruritus, increased serum bile acid (BA) levels and normal gamma-glutamyl transpeptidase activity. Liver histology showed canalicular cholestasis, mild to moderate fibrosis and ultrastructural abnormalities of bile canaliculi. Portal fibrosis progressed in 5 patients. No mutation in ABCB11/BSEP or ATP8B1/FIC1 genes were identified. Immunohistochemical studies demonstrated abnormal cytoplasmic distribution of MYO5B, RAB11A and BSEP in hepatocytes. Interruption of enterohepatic BA cycling after partial external biliary diversion or graft removal proved the most effective to ensure long-term remission. Conclusion: MVID patients are at risk of developing a PFIC-like liver Disease that may hamper outcome after ITx. Our results suggest that cholestasis in MVID patients results from: (i) impairment of the MYO5B/RAB11A apical recycling endosome pathway in hepatocytes (ii) altered targeting of BSEP to the canalicular membrane (iii) and increased ileal BA absorption. Because cholestasis worsens after ITx, indication of a combined liver-ITx should be discussed in MVID patients with severe cholestasis. Future studies will need to address more specifically the impact of MYO5B dysfunction in BA homeostasis. (Hepatology 2013;).
Emmanuel Gonzales - One of the best experts on this subject based on the ideXlab platform.
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myo5b mutations cause cholestasis with normal serum gamma glutamyl transferase activity in children without Microvillous Inclusion Disease
Hepatology, 2017Co-Authors: Emmanuel Gonzales, Sarah A Taylor, Anne Davitspraul, Alice Thebaut, Nadege Thomassin, Catherine Guettier, Peter F Whitington, Emmanuel JacqueminAbstract:Some patients with microvillus Inclusion Disease due to myosin 5B (MYO5B) mutations may develop cholestasis characterized by a progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity. So far MYO5B deficiency has not been reported in patients with such a cholestasis phenotype in the absence of intestinal Disease. Using a new-generation sequencing approach, we identified MYO5B mutations in five patients with progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity without intestinal Disease. Conclusion: These data show that MYO5B deficiency may lead to isolated cholestasis and that MYO5B should be considered as an additional progressive familial intrahepatic cholestasis gene. (Hepatology 2017;65:164-173).
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MYO5B mutations cause cholestasis with normal serum gamma‐glutamyl transferase activity in children without Microvillous Inclusion Disease
Hepatology (Baltimore Md.), 2016Co-Authors: Emmanuel Gonzales, Sarah A Taylor, Alice Thebaut, Nadege Thomassin, Catherine Guettier, Peter F Whitington, Anne Davit-spraul, Emmanuel JacqueminAbstract:Some patients with microvillus Inclusion Disease due to myosin 5B (MYO5B) mutations may develop cholestasis characterized by a progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity. So far MYO5B deficiency has not been reported in patients with such a cholestasis phenotype in the absence of intestinal Disease. Using a new-generation sequencing approach, we identified MYO5B mutations in five patients with progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity without intestinal Disease. Conclusion: These data show that MYO5B deficiency may lead to isolated cholestasis and that MYO5B should be considered as an additional progressive familial intrahepatic cholestasis gene. (Hepatology 2017;65:164-173).
Anne Davitspraul - One of the best experts on this subject based on the ideXlab platform.
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myo5b mutations cause cholestasis with normal serum gamma glutamyl transferase activity in children without Microvillous Inclusion Disease
Hepatology, 2017Co-Authors: Emmanuel Gonzales, Sarah A Taylor, Anne Davitspraul, Alice Thebaut, Nadege Thomassin, Catherine Guettier, Peter F Whitington, Emmanuel JacqueminAbstract:Some patients with microvillus Inclusion Disease due to myosin 5B (MYO5B) mutations may develop cholestasis characterized by a progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity. So far MYO5B deficiency has not been reported in patients with such a cholestasis phenotype in the absence of intestinal Disease. Using a new-generation sequencing approach, we identified MYO5B mutations in five patients with progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity without intestinal Disease. Conclusion: These data show that MYO5B deficiency may lead to isolated cholestasis and that MYO5B should be considered as an additional progressive familial intrahepatic cholestasis gene. (Hepatology 2017;65:164-173).
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myo5b and bile salt export pump contribute to cholestatic liver disorder in Microvillous Inclusion Disease
Hepatology, 2014Co-Authors: Florence Lacaille, Muriel Girard, Virginie Verkarre, Raphael Mategot, Gerard Feldmann, Alain Grodet, Frédérique Sauvat, Sabine Irtan, Anne DavitspraulAbstract:Microvillous Inclusion Disease (MVID) is a congenital disorder of the enterocyte related to mutations in the MYO5B gene, leading to intractable diarrhea often necessitating intestinal transplantation (ITx). Among our cohort of 28 MVID patients, 8 developed a cholestatic liver Disease akin to progressive familial intrahepatic cholestasis (PFIC). Our aim was to investigate the mechanisms by which MYO5B mutations affect hepatic biliary function and lead to cholestasis in MVID patients. Clinical and biological features and outcome were reviewed. Pretransplant liver biopsies were analyzed by immunostaining and electron microscopy. Cholestasis occurred before (n = 5) or after (n = 3) ITx and was characterized by intermittent jaundice, intractable pruritus, increased serum bile acid (BA) levels, and normal gamma-glutamyl transpeptidase activity. Liver histology showed canalicular cholestasis, mild-to-moderate fibrosis, and ultrastructural abnormalities of bile canaliculi. Portal fibrosis progressed in 5 patients. No mutation in ABCB11/BSEP or ATP8B1/FIC1 genes were identified. Immunohistochemical studies demonstrated abnormal cytoplasmic distribution of MYO5B, RAB11A, and BSEP in hepatocytes. Interruption of enterohepatic BA cycling after partial external biliary diversion or graft removal proved the most effective to ensure long-term remission. Conclusion: MVID patients are at risk of developing a PFIC-like liver Disease that may hamper outcome after ITx. Our results suggest that cholestasis in MVID patients results from (1) impairment of the MYO5B/RAB11A apical recycling endosome pathway in hepatocytes, (2) altered targeting of BSEP to the canalicular membrane, and (3) increased ileal BA absorption. Because cholestasis worsens after ITx, indication of a combined liver ITx should be discussed in MVID patients with severe cholestasis. Future studies will need to address more specifically the effect of MYO5B dysfunction in BA homeostasis. (Hepatology 2014;60:301–310)
Gabriel M. Groisman - One of the best experts on this subject based on the ideXlab platform.
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CD10: a valuable tool for the light microscopic diagnosis of Microvillous Inclusion Disease (familial Microvillous atrophy).
The American journal of surgical pathology, 2002Co-Authors: Gabriel M. Groisman, Mary Amar, Erella LivneAbstract:Microvillous Inclusion Disease (MID) is a specific disorder of the intestinal brush border that leads to intractable secretory diarrhea in infants. At present, electron microscopic analysis is required for its definitive diagnosis. However, this technique is not always available or feasible, and the diagnostic Microvillous Inclusions may not be evident in all specimens. Accordingly, the availability of a panel of histochemical and immunohistochemical stains displaying a specific staining pattern for MID will allow pathologists to reach a definitive diagnosis of this disorder without recourse to electron microscopy. CD10 is a membrane-associated neutral peptidase, shown to have a linear brush-border staining pattern in normal small intestine. We studied the staining pattern of CD10 in small intestinal biopsies from six patients with MID and in 24 control cases (10 normal small intestine, 10 celiac Disease, two autoimmune enteropathy, and two allergic enteropathy). All MID cases revealed prominent cytoplasmic CD10 immunoreactivity in surface enterocytes. In contrast, all control cases showed linear brush-border staining. Similar results were obtained with periodic acid-Schiff, polyclonal carcinoembryonic antigen, and alkaline phosphatase, three stains known to show cytoplasmic staining of surface enterocytes in MID. In conclusion, CD10 is a valuable tool for the diagnosis of MID. It may be used as part of a panel that includes other stains with a distinctive staining pattern in MID such as periodic acid-Schiff, polyclonal carcinoembryonic antigen, and alkaline phosphatase. We suggest that the definitive diagnosis of MID can be reached when small bowel biopsies from infants with intractable diarrhea display cytoplasmic staining of surface enterocytes with the above-mentioned stains.
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Enterocyte apoptosis and proliferation are increased in Microvillous Inclusion Disease (familial Microvillous atrophy).
Human pathology, 2000Co-Authors: Gabriel M. Groisman, Edmond Sabo, Alona Meir, Sylvie Polak-charconAbstract:Microvillous Inclusion Disease (MID) is characterized by diffuse villous atrophy without inflammatory changes. While increased apoptosis has been related to mucosal flattening in celiac Disease, the role of apoptosis in the pathogenesis of MID is unknown. The aim of this study was to assess the rates of apoptosis and cell proliferation in MID and to compare them with those of normal controls and celiac Disease. Small intestinal biopsies from 5 infants with MID, 10 children with normal villous architecture, and 10 children with untreated celiac Disease were stained with the terminal uridine deoxynucleotidyl nick end labeling (TUNEL) method to assess apoptotic activity, and with Ki-67 immunchistochemistry to assess cellular proliferation. TUNEL and Ki-67 positive enterocytes were counted in a minimum of 20 well oriented half crypts per section. The percentage of apoptotic cells per crypt (apoptotic index) in normal, MID, and celiac biopsies was 0.03 ± 0.01%, 0.08 ± 0.08%, and 0.16 ± 0.3%, respectively. Significant differences were found between normal and MID, and between normal and celiac cases. The percentage of Ki-67 positive cells per crypt (proliferation index) in normal, MID, and celiac cases was 14 ± 2.5%, 28 ± 9.2%, and 56 ± 14%. Significant differences were found between the 3 groups. In conclusion, (1) enterocyte apoptosis and proliferation are increased in MID; (2) apoptosis appears to be an important factor of cell loss and may be, at least in part, responsible for villous atrophy in MID; and (3) crypts in MID are hyperplastic and not hypoplastic.
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The value of polyclonal carcinoembryonic antigen immunostaining in the diagnosis of Microvillous Inclusion Disease
Human pathology, 1993Co-Authors: Gabriel M. Groisman, Ofer Ben-izhak, Audrey H. Schwersenz, Moshe Berant, Billie FyfeAbstract:Microvillous Inclusion Disease is a specific disorder recognized as a cause of intractable diarrhea of infancy. We studied three cases by light microscopy, electron microscopy, and immunostaining for polyclonal carcinoembryonic antigen (CEA). Histologically, all cases had villous atrophy and abnormal accumulation of periodic acid-Schiff-positive material in surface enterocytes. Ultrastructurally, poorly developed brush-border and intracytoplasmic Inclusions lined by intact microvilli were present in surface enterocytes. Crypt cells showed well-preserved surface microvilli. Carcinoembryonic antigen immunostaining showed prominent intracytoplasmic reactivity in surface enterocytes and linear brush-border reactivity in crypt cells. Normal and Diseased small bowel biopsy specimens used as controls revealed linear brush-border reactivity without intracytoplasmic staining. Intracytoplasmic positivity for carcinoembryonic antigen in Microvillous Inclusion Disease is explained by its presence in the glycocalyx within the Microvillous Inclusions. The demonstration of a distinct staining pattern for polyclonal carcinoembryonic antigen in routinely processed small bowel biopsy specimens provides a new useful criterion that complements other established techniques for accurate diagnosis of Microvillous Inclusion Disease.
Sarah A Taylor - One of the best experts on this subject based on the ideXlab platform.
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myo5b mutations cause cholestasis with normal serum gamma glutamyl transferase activity in children without Microvillous Inclusion Disease
Hepatology, 2017Co-Authors: Emmanuel Gonzales, Sarah A Taylor, Anne Davitspraul, Alice Thebaut, Nadege Thomassin, Catherine Guettier, Peter F Whitington, Emmanuel JacqueminAbstract:Some patients with microvillus Inclusion Disease due to myosin 5B (MYO5B) mutations may develop cholestasis characterized by a progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity. So far MYO5B deficiency has not been reported in patients with such a cholestasis phenotype in the absence of intestinal Disease. Using a new-generation sequencing approach, we identified MYO5B mutations in five patients with progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity without intestinal Disease. Conclusion: These data show that MYO5B deficiency may lead to isolated cholestasis and that MYO5B should be considered as an additional progressive familial intrahepatic cholestasis gene. (Hepatology 2017;65:164-173).
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MYO5B mutations cause cholestasis with normal serum gamma‐glutamyl transferase activity in children without Microvillous Inclusion Disease
Hepatology (Baltimore Md.), 2016Co-Authors: Emmanuel Gonzales, Sarah A Taylor, Alice Thebaut, Nadege Thomassin, Catherine Guettier, Peter F Whitington, Anne Davit-spraul, Emmanuel JacqueminAbstract:Some patients with microvillus Inclusion Disease due to myosin 5B (MYO5B) mutations may develop cholestasis characterized by a progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity. So far MYO5B deficiency has not been reported in patients with such a cholestasis phenotype in the absence of intestinal Disease. Using a new-generation sequencing approach, we identified MYO5B mutations in five patients with progressive familial intrahepatic cholestasis-like phenotype with normal serum gamma-glutamyl transferase activity without intestinal Disease. Conclusion: These data show that MYO5B deficiency may lead to isolated cholestasis and that MYO5B should be considered as an additional progressive familial intrahepatic cholestasis gene. (Hepatology 2017;65:164-173).