title: Peutz-Jeghers syndrome: early clinical expression of a new STK11 gene variant.
abstract: Genetic heterogeneity has been recognised in Peutz-Jeghers syndrome (PJS) (over 230 STK11 gene mutations reported). We report a rare PJS phenotype with early extensive gastrointestinal (GI) presentation and a new genetic variant. The case presented as haematochezia and mucocutaneous pigmentation (the patient was 3 years of age). Endoscopy showed several polyps throughout the stomach/colon (PJ-type hamartomas); the larger polyps were resected. Small bowel imaging detected multiple jejunum/ileum small polyps. During 8 years of follow-up of this asymptomatic patient, an increasing number of diffusely distributed polyps was observed and polypectomies were performed. Subsequently, the patient failed consultations; when the patient was 13 years of age, emergency surgery was required due to small bowel intussusception (ileal polyp). A STK11 gene study identified two missense variants in heterozygous (yet unknown significance but probably pathogenic): c.854T>A (exon 6) and c.446C>T* (exon 2) (*not previously reported). We report two STK11 gene variants (one not previously described) of yet undetermined causality in a paediatric patient presenting with extensive GI involvement at a very early age, with no family medical history. Structural and functional repercussion of the newly described variants should be further investigated.
authors.affiliation: Gastroenterology Unit, Paediatric Department, Hospital Santa Maria, Lisbon, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Brito
authors.affiliation: Gastroenterology Unit, Paediatric Department, Hospital Santa Maria, Lisbon, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Póvoas
authors.affiliation: Genetics Service, Paediatric Department, University Hospital Santa Maria, Lisbon, Portugal.
authors.forename: Juliette
authors.initials: J
authors.lastname: Dupont
authors.affiliation: Gastroenterology Unit, Paediatric Department, Hospital Santa Maria, Lisbon, Portugal Gastroenterology Unit, Department of Pediatrics, University Hospital Santa Maria, Medical Faculty of Lisbon, Lisbon, Portugal.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Lopes
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003106:Colon / Q000473:pathology; D003111:Colonic Polyps / Q000235:genetics; D005091:Exons; D014644:Genetic Variation; D006801:Humans; D007077:Ileal Diseases / Q000235:genetics; D007421:Intestine, Small / Q000473:pathology; D007443:Intussusception / Q000235:genetics; D008297:Male; D020125:Mutation, Missense; D010580:Peutz-Jeghers Syndrome / Q000150:complications / Q000235:genetics*; D010641:Phenotype; D011127:Polyps / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013270:Stomach / Q000473:pathology
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases