Article
Genetics & Heredity
Yusriya Al Rawahi, Omar Al Sunaidi, Mohammed Al-Masqari, Adawiya Al Jamei, Dafalla Rahamtalla, Almundher Al-Maawali
Summary: Biallelic SPINT2 pathogenic variants can cause congenital diarrhea and enteropathy, but this study reported a case where the patient only presented with diarrhea symptoms and had no additional extra-intestinal features. The patient was found to have a novel homozygous variant in the SPINT2 gene, and in vitro functional studies confirmed the loss of inhibitory activity of intestinal serine proteases caused by this variant.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Gastroenterology & Hepatology
Yougen Zhan, Stephen C. Ward, Maria Isabel Fiel, Julie Teruya-Feldstein, Eileen M. McKay, Fumiko Dekio
Summary: The study found disrupted apical-basal polarity of cholangiocytes and ductopenia in patients with Tufting enteropathy (TE). EpCam was shown to play a role in maintaining the integrity of biliary epithelium, and there was evidence of disrupted development of hepatic reparative cells in TE patients.
LIVER INTERNATIONAL
(2021)
Article
Pediatrics
Hasret Ayyildiz Civan, Coleen Leitner, Iris Oestreicher, Anna-Maria Schneider, Malte Cremer, Johannes A. Mayr, Rainer Rossi, Thomas Mueller, Andreas R. Janecke
Summary: Tufting enteropathy is caused by recessive EPCAM mutations, resulting in congenital diarrhea and disorganization of enterocytes. The study found that patients with TE experienced adequate weight gain with PN but often had stunted growth, with diagnosis typically being delayed.
Review
Medicine, General & Internal
Barun Das, Mamata Sivagnanam
Summary: Congenital tufting enteropathy (CTE) is an autosomal recessive disease of infancy that causes severe intestinal failure, and insight into the pathogenesis and predicted mechanisms of the disease may contribute to future therapeutic options.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Genetics & Heredity
Julia Ernst, Jamila Hiasat, Michelle L. Alabek, Hannah L. Scanga, William Motley, Ken K. Nischal
Summary: A 5-year-old girl with treatment-refractory dry eye and eye pain episodes was diagnosed with SCSD, receiving eye examination under anesthesia and punctal plug placement. The first case report documenting OCT imaging and corneal photographs in a SCSD patient expands the ophthalmic phenotype of this rare genetic disorder.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Gastroenterology & Hepatology
Barun Das, Kevin Okamoto, John Rabalais, Jocelyn A. Young, Kim E. Barrett, Mamata Sivagnanam
Summary: Mutant mice with CTE-associated EpCAM mutations showed altered intestinal cell differentiation, leading to an increase in absorptive cells at the expense of major secretory cells. Although the proportion of absorptive enterocytes increased, they lacked key functional properties, underlying pathogenic features of CTE such as malabsorption and diarrhea. Treatment with a Notch signaling inhibitor increased the numbers of major secretory cell types in mutant enteroids.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Pathology
Sonja Chen, Jeffrey D. Goldsmith, Rima Fawaz, Alyaa Al-Ibraheemi, Antonio R. Perez-Atayde, Sara O. Vargas
Summary: Congenital tufting enteropathy (CTE) is a rare heritable cause of intractable diarrhea due to EPCAM mutation. In affected patients, absent intestinal epithelial cell adhesion molecule (EpCAM) expression results in loss of MOC31 immunostaining. Hepatopathy in CTE patients may be difficult to separate from comorbid disease, but absent ductular reaction may be characteristic.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2021)
Article
Pediatrics
Shooq Alkhalifa, Aysha Darwish, Mohamed Awadh, Salman M. M. Alkhalifa, Abdulla Darwish
Summary: Congenital tufting enteropathy (CTE) is a rare autosomal recessive disorder caused by EPCAM gene mutation. It presents in early infancy as intractable diarrhea independent of breast or formula feeding, requiring life-long total parental nutrition or small bowel transplantation in severe cases. This study aims to review the literature on CTE, discuss its clinicopathological aspects, and distinguish it from other causes of congenital diarrheal disorders (CDDs).
CASE REPORTS IN PEDIATRICS
(2023)
Review
Physiology
Nouf J. Althali, Kathryn E. Hentges
Summary: Congenital heart defects refer to structural abnormalities of the heart or blood vessels present at birth, affecting approximately 1% of newborns worldwide. Tetralogy of Fallot is the most common cyanotic congenital heart abnormality, accounting for 5-10% of all congenital cardiac defects. While some cases of TOF are associated with known diseases or chromosomal abnormalities, the majority are non-syndromic and have unknown causes.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Genetics & Heredity
Katalin Komlosi, Olivier Claris, Sophie Collardeau-Frachon, Julia Kopp, Ingrid Hausser, Juliette Mazereeuw-Hautier, Nathalie Jonca, Andreas D. Zimmer, Damien Sanlaville, Judith Fischer
Summary: The cases highlight the phenotypic variability of glycosylation disorders, emphasizing the importance of broadening the differential diagnosis of ichthyosis and actively searching for organ involvement in neonates with ichthyosis. The report describes two neonatal cases of lethal ichthyosis from the same family, caused by compound heterozygous variants in the DOLK gene.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Weihui Yan, Yongtao Xiao, Yunyi Zhang, Yijing Tao, Yi Cao, Kunhui Liu, Wei Cai, Ying Wang
Summary: This study enhances our understanding of the clinical manifestations and molecular genetics of neonatal-onset watery diarrhea. Early diagnosis through genomic analysis is possible for infants with atypical histological features. The discovery of novel mutations in the EPCAM and MYO5B genes provides further evidence for the association of genetic mutations with neonatal-onset diarrhea, with c.269_270 dupAA being the most frequent SLC26A3 mutation in China to date.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Gastroenterology & Hepatology
Olivier Goulet, Benedicte Pigneur, Fabienne Charbit-Henrion
Summary: Congenital enteropathies are rare inherited diseases that typically occur early in life and involve defects in enterocyte structure or differentiation, leading to severe intestinal failure. The diagnostic approach is based on clinical presentation and histopathological analyses, with treatment options including dietary interventions and long-term parenteral nutrition or intestinal transplantation.
BEST PRACTICE & RESEARCH CLINICAL GASTROENTEROLOGY
(2022)
Article
Clinical Neurology
Alicia Wang, A. Eliot Shearer, Guang Wei Zhou, Margaret Kenna, Dennis Poe, Greg R. Licameli, Jacob R. Brodsky
Summary: Hearing loss is often accompanied by peripheral vestibular loss, which can impact motor development and quality of life in children. The extent of vestibular dysfunction in genetic pediatric hearing loss is not well-understood. Research in children with genetic hearing loss undergoing vestibular evaluation found that PVL is common and varies by affected gene.
FRONTIERS IN NEUROLOGY
(2021)
Article
Genetics & Heredity
Celia Fernandez-Alcalde, Maria Nieves-Moreno, Susana Noval, Jesus M. Peralta, Victoria E. E. Montano, Angela del Pozo, Fernando Santos-Simarro, Elena Vallespin
Summary: Next-generation sequencing was used to identify mutations causing non-syndromic congenital cataracts, with a detection rate of 49% and most mutations being de novo and autosomal dominant. Mutations in crystallin and membrane protein genes were commonly found.
Article
Genetics & Heredity
Leticia Alves da Rocha, Lucas Vieira Lacerda Pires, Guilherme Lopes Yamamoto, Jose Ricardo Magliocco Ceroni, Rachel Sayuri Honjo, Edgard de Novaes Franca Bisneto, Luiz Antonio Nunes Oliveira, Carla Rosenberg, Ana Cristina Victorino Krepischi, Maria Rita Passos-Bueno, Chong Ae Kim, Debora Romeo Bertola
Summary: Congenital limb deficiency (CLD) is a common congenital anomaly characterized by underdevelopment or absence of one or more limb bones, with diverse causes including genetic and environmental factors. Genetic investigations using advanced techniques like next-generation sequencing (NGS) have shown a diagnostic yield of 45.7%, with potential for identifying new variants and expanding the understanding of the phenotypic spectrum in these disorders.
Article
Gastroenterology & Hepatology
Sascha Cording, Ludovic Lhermitte, Georgia Malamut, Sofia Berrabah, Amelie Trinquand, Nicolas Guegan, Patrick Villarese, Sophie Kaltenbach, Bertrand Meresse, Sherine Khater, Michael Dussiot, Marc Bras, Morgane Cheminant, Bruno Tesson, Christine Bole-Feysot, Julie Bruneau, Thierry Jo Molina, David Sibon, Elizabeth Macintyre, Olivier Hermine, Christophe Cellier, Vahid Asnafi, Nadine Cerf-Bensussan
Summary: The study identified mutations activating the JAK1-STAT3 pathway as the main drivers of enteropathy-associated T-cell lymphoma, potentially in combination with mutations in negative regulators of NF-kappa B. These mutations could promote the clonal emergence of malignant lymphocytes in the cytokine-rich coeliac intestine, and are attractive therapeutic targets for treating refractory celiac disease and blocking progression towards EATL.
Article
Genetics & Heredity
Fabienne Charbit-Henrion, Roman Goguyer-Deschaumes, Keren Borensztajn, Marc Mirande, Jeremy Berthelet, Fernando Rodrigues-Lima, Anis Khiat, Marie-Louise Fremond, Brigitte Bader-Meunier, Marco M. Rodari, Luis Seabra, Gillian Rice, Marie Legendre, David Drummond, Laureline Berteloot, Charles-Joris Roux, Nathalie Boddaert, Philippe Drabent, Thierry Jo Molina, Florence Lacaille, Manoelle Kossorotoff, Nadine Cerf-Bensussan, Marianna Parlato, Alice Hadchouel
Summary: Variants in aminoacyl-tRNA synthetases (ARSs) genes are associated with a wide range of human inherited diseases, with defective PheRS leading to symptoms like brain abnormalities. Furthermore, FARSA deficiency can cause inflammation and autoimmunity, with JAK inhibition showing improvement in lung disease.
Article
Biochemistry & Molecular Biology
Qing Nian, Jeremy Berthelet, Marianna Parlato, Ariel E. Mechaly, Rongxing Liu, Jean-Marie Dupret, Nadine Cerf-Bensussan, Ahmed Haouz, Fernando Rodrigues Lima
Summary: PTPN2 is an important protein tyrosine phosphatase involved in cell signaling, with its structural analysis still poorly documented; the crystal structure of a pathogenic mutant Cys216Gly has been reported, showing that it retains some functionality, which could provide insights into the structural impacts of pathogenic mutations in PTPN2.
Editorial Material
Gastroenterology & Hepatology
Fabienne Charbit-Henrion, Manon Haas, Stanislas Chaussade, Christophe Cellier, Nadine Cerf-Bensussan, Georgia Malamut
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Anais Levescot, Georgia Malamut, Nadine Cerf-Bensussan
Summary: Coeliac disease is an immune enteropathy induced by genetic and environmental factors. The antigluten immune response and epithelial damage are key events in its pathogenesis, with the JAK/STAT pathway playing a crucial role. However, there are still many unanswered questions and challenges, such as the variability of the disease and improving the patients' quality of life.
Article
Genetics & Heredity
Ema Bogdanic, Thomas Mueller, Peter Heinz-Erian, Dorota Garczarczyk-Asim, Andreas R. Janecke, Aline Rueckel
Summary: This study reported a patient with congenital sodium diarrhea, identified novel compound heterozygous variants in the SLC9A3 gene, and indicated that the clinical phenotype of the patient is milder compared to known CSD spectrum.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2022)
Article
Pediatrics
Anna M. Kavallar, Franka Messner, Stefan Scheidl, Rupert Oberhuber, Stefan Schneeberger, Denise Aldrian, Valeria Berchtold, Murat Sanal, Andreas Entenmann, Simon Straub, Anna Gasser, Andreas R. Janecke, Thomas Mueller, Georg F. Vogel
Summary: This case report presents three cases of PFIC1 patients who underwent LT and successfully resolved graft inflammation and steatosis by using terminal ileum SBD.
Article
Immunology
Marco M. M. Rodari, Dominique Cazals-Hatem, Mathieu Uzzan, Nicolas Martin Silva, Anis Khiat, Minh Chau Ta, Ludovic Lhermitte, Aurore Touzart, Sylvain Hanein, Clea Rouillon, Francisca Joly, Adrienne Elmorjani, Julie Steffann, Nadine Cerf-Bensussan, Marianna Parlato, Fabienne Charbit-Henrion
Summary: This study demonstrates that impaired regulation of SOCS1 can lead to a wide range of intestinal manifestations, emphasizing the need for genetic screening and considering the use of JAK inhibitors in severe treatment-refractory enteropathies.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Cell & Tissue Engineering
Celine Banal, Eddy Quelennec, Cecile Talbotec, Anis Khiat, Fabienne Charbit-Henrion, Nadine Cerf-Bensussan, Nathalie Lefort, Corinne Lebreton
Summary: Mutations in UNC45A can cause a syndrome with symptoms including cholestasis, diarrhea, hearing loss, and bone fragility. We created iPSCs from a patient with a homozygous missense mutation in UNC45A using integration-free Sendal virus, and these cells showed normal karyotype, expressed pluripotency markers, and were able to differentiate into the three germ cell layers.
STEM CELL RESEARCH
(2023)
Article
Genetics & Heredity
Julia Vodopiutz, Lisa-Maria Steurer, Florentina Haufler, Franco Laccone, Dorota Garczarczyk-Asim, Matthias Hilkenmeier, Philipp Steinbauer, Andreas R. Janecke
Summary: SHOX deficiency is a common genetic cause of short stature. It can lead to Leri-Weill dyschondrosteosis and nonspecific short stature. This study reports the pseudo-autosomal recessive inheritance of Leri-Weill dyschondrosteosis in two siblings caused by a novel homozygous non-canonical splice-site variant in the SHOX gene. This study expands the understanding of the molecular and inheritance spectrum of SHOX deficiency.
Article
Genetics & Heredity
Ferda O. Hosnut, Andreas R. Janecke, Gulseren Sahin, Georg F. Vogel, Naz G. Lafci, Paul Bichler, Thomas Mueller, Lukas A. Huber, Taras Valovka, Aysel U. Aksu
Summary: Congenital glucose-galactose malabsorption is a rare autosomal recessive disorder caused by mutations in SLC5A1 gene. Our study reports clinical and molecular data from 11 affected individuals in four unrelated Turkish families. Two novel SLC5A1 missense variants, p.Gly43Arg and p.Ala92Val, were identified in two families and linked to the disease. Our findings expand the mutational spectrum of this rare disorder.
Article
Gastroenterology & Hepatology
Annick Hamon, Dominique Cazals-Hatem, Carmen Stefanescu, Mathieu Uzzan, Xavier Treton, Alain Sauvanet, Yves Panis, Marie Monsinjon, Fanny Bonvalet, Olivier Corcos, Emilie Azouguene, Nadine Cerf-Bensussan, Yoram Bouhnik, Fabienne Charbit-Henrion
Summary: This article reports the case of two French female siblings with CEAS related to SLCO2A1 mutations. Next-generation sequencing identified two compound heterozygous variants in the SLCO2A1 gene in one sister, which were also present in the other sister. This study suggests that CEAS may not be exclusive to Asian populations and should be considered in European patients with intractable recurrent ulcerations of the small intestine mimicking Crohn's disease.
JOURNAL OF CROHNS & COLITIS
(2023)
Article
Medicine, Research & Experimental
Remi Duclaux-Loras, Corinne Lebreton, Jeremy Berthelet, Fabienne Charbit-Henrion, Ophelie Nicolle, Celine Revenu de Courtils, Stephanie Waich, Taras Valovka, Anis Khiat, Marion Rabant, Caroline Racine, Ida Chiara Guerrera, Julia Baptista, Maxime M. Mahe, Michael W. Hess, Beatrice Durel, Nathalie Lefort, Celine Banal, Melanie Parisot, Cecile Talbotec, Florence Lacaille, Emmanuelle Ecochard-Dugelay, Arzu Meltem Demir, Georg F. Vogel, Laurence Faivre, Astor Rodrigues, Darren Fowler, Andreas R. Janecke, Thomas Mueller, Lukas A. Huber, Fernando Rodrigues-Lima, Frank M. Ruemmele, Holm H. Uhlig, Filippo Del Bene, Gregoire Michaux, Nadine Cerf-Bensussan, Marianna Parlato
Summary: Variants in the UNC45A cochaperone can cause a syndrome with symptoms including diarrhea, cholestasis, deafness, and bone fragility. This study provides evidence that UNC45A plays a crucial role in epithelial morphogenesis and its loss can lead to a variant of microvillus inclusion disease.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Meeting Abstract
Gastroenterology & Hepatology
G. Malamut, M. Simon, M. Nachury, M. Uzzan, M. Serrero, M. Fumery, C. Trang-Poisson, C. Zallot, V. Abitbol, F. Charbit-Henrion, J. M. Gornet, C. Picard, N. Cerf-Bensussan, S. Chaussade, H. Sokol
JOURNAL OF CROHNS & COLITIS
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Alban Ziegler, Remi Duclaux-Loras, Celine Revenu, Bernadette Begue, Karine Duroure, Linda Grimaud, Anne Laure Guihot, Valerie Desquiret Dumas, Mohammed Zarhrate, Emmanuel Mas, Anne Breton, Thomas Edouard Edouard, Clarisse Billon, Michael Frank, Estelle Colin, Guy Lenaers, Daniel Henrion Henrion, Stanislas Lyonnet, Laurence Faivre, Yves Alembik, Anais Philippe, Bruno Moulin, Eyal Reinstein Reinstein, Shay Tzur, Ruben Attali, George McGillivray, Susan M. White, Lyndon Gallacher, Kerstin Kutsche, Pauline Schneeberger, Katta M. Girisha, Shalini S. Nayak, Lynn Pais, Reza Maroofian, Barbara Vona Vona, Ehsan Ghayoor Karmiani Karmiani, Caroline Lekszas Lekszas, Thomas Haaf, Ludovic Martin, Frank Ruemmele, Dominique Bonneau, Nadine Cerf-Bensussan, Filippo Del Bene Del Bene, Marianna Parlato
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)