ABCMdb

PMID: 10801389

Gomez Lira M, Benetazzo MG, Marzari MG, Bombieri C, Belpinati F, Castellani C, Cavallini GC, Mastella G, Pignatti PF
High frequency of cystic fibrosis transmembrane regulator mutation L997F in patients with recurrent idiopathic pancreatitis and in newborns with hypertrypsinemia.
Am J Hum Genet. 2000 Jun;66(6):2013-4., [PubMed]

Sentences

No. Mutations Sentence Comment

12 ABCC7 p.Arg553* ABCC7 p.Gly542* ABCC7 p.Phe1052Val ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe Among these rare mutations, L997F was identified in 4 (12.5%) of 32 patients with idiopathic pancreatitis (genotypes L997F/DF508, L997F/5T, and twice L997F/no mutation identified, respectively), and in 4 (8%) of 49 newborns with hypertrypsinemia (genotypes L997F/G542X, L997F/R553X, L997F/DF508, and L997F-F1052V phase unknown, respectively). Login to comment 13 ABCC7 p.Leu997Phe The cumulative frequency of the L997F mutation in pancreatic dysfunction (8 [9.87%] of 81) is significantly higher than that found in normal control individuals (Bombieri et al. 1998, 2000, and unpublished data) from the same population (3 [0.97%] of 315; Fisher`s exact test, P = ; odds ratio 11.397 (range 2.95-44.029). Login to comment 15 ABCC7 p.Leu997Phe L997F was initially reported as a DNA variant (Fanen et al. 1992) and was described in a 5-year-old boy from northern India who presented a borderline sweat chloride value and features highly suggestive of CF (Cystic Fibrosis Genetic Analysis Consortium) and in patients with disseminated bronchiectasis (Bombieri et al. 2000, Girodon et al. 1997). Login to comment 16 ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe Following the guidelines of a recent consensus statement on the diagnosis of CF (Rosenstein et al. 1998), we tested for L997F in 100 carriers of mutation DF 508 (mothers of typical patients with CF) from the same population as the individuals with pancreatitis and hypertrypsinemia; since none of them carried it, L997F is designated as a CF-causing mutation, according to criterion number 4 in the above-cited article (Rosenstein et al. 1998). Login to comment 17 ABCC7 p.Arg553* ABCC7 p.Gly542* ABCC7 p.Leu997Phe This classification implies that the L997F heterozygotes compounded with common CF mutations found among the patients with idiopathic pancreatitis (DF508) and that the hypertrypsinemic newborns with negative sweat chloride (DF508, G542X, and R553X) should be diagnosed as affected by an atypical form of CF; a close follow-up is indicated for these patients. Login to comment 18 ABCC7 p.Leu997Phe In conclusion, these data indicate that CFTR Letters to the Editor L997F is associated with increased susceptibility to pancreatic ductular obstruction. Login to comment