Isolated idiopathic chronic pancreatitis associated with a compound heterozygosity for two mutations of the CFTR gene Marie-Pierre REBOUL (1), David LAHARIE (2), Michel AMOURETTI (2), Didier LACOMBE (1), Albert IRON (1) (1) Service de Génétique Médicale, Hôpital Pellegrin, Bordeaux ; (2) Département d’Hépato-Gastroentérologie, Hôpital Haut-Levêque, Pessac. SUMMARY We report the case of a patient suffering from idiopathic chronic pancreatitis (ICP) and compound heterozygous for mutations G542X and S1235R of the cystic fibrosis transmembrane regulator (CFTR) gene. The patient had normal sweat test and no other clinical sign usually linked with a typical or moderate pathology (bronchiectasis, nasal polyposis, congenital absence of the vas deferens) of the CFTR gene. G542X is a severe mutation, which is usually found in classical cystic fibrosis when associated with other severe mutations. S1235R is a quite rare abnormality recently reported as being potentially pathogenic when combined in trans with a second CF mutation. Our case is quite similar to the only other six patients in the literature in whom only the pancreas is affected and who bear a rare mutation with moderate effect. The history and the clinical features of our patient indicate an unambiguous isolated ICP in which the presence of the S1235R mutation — in trans with regard to G542X — is likely responsible for the ICP phenotype. This case could throw light on some of the as yet poorly known abnormalities of the CFTR gene in the ICP phenotype. RE ´ SUME ´ Pancréatite chronique idiopathique isolée associée à une hétérozygotie composite pour deux mutations du gène CFTR Marie-Pierre REBOUL, David LAHARIE, Michel AMOURETTI, Didier LACOMBE, Albert IRON (Gastroenterol Clin Biol 2003;27:821-824) Nous rapportons le cas d’un malade souffrant de pancréatite chronique idiopathique (PCI) hétérozygote composite pour les mutations G542X et S1235R du gène CFTR. Le malade avait un test sudoral normal et pas d’autre signe clinique associé habituellement à une affection (bronchectasie, polypose nasale, agénésie des canaux déférent) associée aux mutations du gène CFTR. G542X est une mutation sévère rencontrée assez fréquemment — en association avec d’autres mutations sévères — dans des formes de mucovisci- dose classique. S1235R est une anomalie assez rare, rapportée récemment comme étant potentiellement délétère quand elle est associée en trans à une autre mutation du gène CFTR. Notre cas est à rapprocher des seuls six malades de la littérature dont l’atteinte semble limitée au pancréas et porteurs d’une mutation rare à effet modéré. L’histoire et le tableau clinique de la maladie chez notre malade évoquent de manière complète et sans ambiguïté une PCI isolée dans laquelle la présence de la mutation S1235R — en position trans par rapport à G542X — est très vraisemblablement responsable du phénotype de pancréatite chronique idiopathique. Ce cas peut contribuer à une meilleure connaissance d’une certaine spécificité d’anomalies — encore mal connues — du gène CFTR dans le phénotype de PCI. M any patients suffering from typical cystic fibrosis (CF; OMIM 219700) present with chronic pancre- atitis secondary to pancreatic lesions similar to those of idiopathic chronic pancreatitis (ICP) [1]. Attention has recently been drawn to ICP patients without known etiology, and the CFTR gene at chromosome 7q31.2 (OMIM 602421) has been implicated in this disease. It would be preferable to investigate only the fraction of patients (about 30%) whose pathology is clearly recognized as recurrent acute pancreatitis or ICP, thereby excluding patients suffering from secondary chronic pancreatitis due to excessive alcohol consumption (i.e. about 70% of patients) and the familial autosomal dominant forms of hereditary pancreatitis (1%) involving the gene encoding for the cationic trypsinogen gene at chromosome 7q35 (HP; OMIM 167, 800) [2]. So far, the mutations and polymorphisms of the CFTR gene have been analyzed in 10 cohorts of patients with chronic pancreatitis [3-12]. Six of these series [4, 5, 7, 8, 11, 12] included only patients with ICP, the other four [3, 6, 9, 10] included patients with both ICP and alcoholic pancreatitis. The majority of these studies show that, among ICP patients, the frequency of CFTR gene mutations is significantly higher (18% overall) than in the general population (4%). Most ICP patients are heterozygous, and 14 are compound heterozygous for two mutations of the CFTR gene. We studied the CFTR gene in a 35-year-old male patient with symptoms limited to the occurrence of iterative episodes of idiopathic pancreatitis. He had an original compound heterozy- gosity for the severe G542X mutation and the mild S1235R mutation. Comparison of the genetic status and clinical pheno- type of our patient with the 14 cases reported so far [4, 5, 7, 11, 12] would throw light on the implication of the CFTR gene in this particular type of chronic pancreatitis. Case report A 33-year-old man was seen for painful epigastric syndrome associated with high levels of serum pancreatic enzymes: hyperamylasemia, 358 U/L (normal, 25-115); hyperlipasemia, 2460 U/L (normal, 114-286); hyperleucocytosis, 19.1 G/L (normal, 4-10). CT scan and MRI confirmed the diagnosis of acute pancreatitis (Balthazar stage E) with diffuse anomalies and calcifications and with inflammatory lesions prevailing in the small pancreas where there was duct dilatation. Cancer of the pancreas and autoimmune pancreatitis were excluded by two Reprints: A. IRON, Service de Génétique Médicale, UF de Biologie Moléculaire, Hôpital Pellegrin-Tripode, 33076 Bordeaux Cedex, France. E-mail: albert.iron@chu-bordeaux.fr © Masson, Paris, 2003. Gastroenterol Clin Biol 2003;27:821-824 821 © 2021 Elsevier Masson SAS. Tous droits réservés. - Document téléchargé le 06/12/2021 Il est interdit et illégal de diffuser ce document.