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Novel Homozygous Inactivating Mutation in the PCSK1 Gene in an Infant with Congenital Malabsorptive Diarrhea.
Aerts, Laetitia; Terry, Nathalie A; Sainath, Nina N; Torres, Clarivet; Martín, Martín G; Ramos-Molina, Bruno; Creemers, John W.
Afiliación
  • Aerts L; Centre of Human Genetics, Laboratory for Biochemical Neuroendocrinology, 3000 KU Leuven, Belgium.
  • Terry NA; Department of Pediatrics, Division of Gastroenterology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Sainath NN; Department of Pediatrics, Division of Gastroenterology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Torres C; Children's National Medical Center, Director Intestinal Rehabilitation Program, Washington, DC 20010, USA.
  • Martín MG; Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA.
  • Ramos-Molina B; Centre of Human Genetics, Laboratory for Biochemical Neuroendocrinology, 3000 KU Leuven, Belgium.
  • Creemers JW; Biomedical Research Institute of Murcia (IMIB-Arrixaca), 30120 Murcia, Spain.
Genes (Basel) ; 12(5)2021 05 10.
Article en En | MEDLINE | ID: mdl-34068683
Proprotein convertase 1/3 (PC1/3), encoded by the PCSK1 gene, is expressed in neuronal and (entero)endocrine cell types, where it cleaves and hence activates a number of protein precursors that play a key role in energy homeostasis. Loss-of-function mutations in PCSK1 cause a recessive complex endocrinopathy characterized by malabsorptive diarrhea and early-onset obesity. Despite the fact that neonatal malabsorptive diarrhea is observed in all patients, it has remained understudied. The aim of this study was to investigate the enteroendocrine pathologies in a male patient with congenital PCSK1 deficiency carrying the novel homozygous c.1034A>C (p.E345A) mutation. This patient developed malabsorptive diarrhea and metabolic acidosis within the first week of life, but rapid weight gain was observed after total parenteral nutrition, and he displayed high proinsulin levels and low adrenocorticotropin. In vitro analysis showed that the p.E345A mutation in PC1/3 resulted in a (near) normal autocatalytic proPC1/3 processing and only partially impaired PC1/3 secretion, but the processing of a substrate in trans was completely blocked. Immunohistochemical staining did not reveal changes in the proGIP/GIP and proglucagon/GLP-1 ratio in colonic tissue. Hence, we report a novel PCSK1 deficient patient who, despite neonatal malabsorptive diarrhea, showed a normal morphology in the small intestine.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proproteína Convertasa 1 / Diarrea / Enfermedades del Sistema Endocrino / Mutación Límite: Humans / Infant / Male Idioma: En Revista: Genes (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proproteína Convertasa 1 / Diarrea / Enfermedades del Sistema Endocrino / Mutación Límite: Humans / Infant / Male Idioma: En Revista: Genes (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Suiza