ABCMdb

PMID: 15857421

Derichs N, Schuster A, Grund I, Ernsting A, Stolpe C, Kortge-Jung S, Gallati S, Stuhrmann M, Kozlowski P, Ballmann M
Homozygosity for L997F in a child with normal clinical and chloride secretory phenotype provides evidence that this cystic fibrosis transmembrane conductance regulator mutation does not cause cystic fibrosis.
Clin Genet. 2005 Jun;67(6):529-31., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Leu997Phe Letter to the Editor Homozygosity for L997F in a child with normal clinical and chloride secretory phenotype provides evidence that this Cystic Fibrosis Transmembrane Conductance Regulator mutation does not cause cystic fibrosis To the Editor: The cystic fibrosis (CF) basic defect is caused by various mutations in the CF transmembrane conductance regulator (CFTR) gene which encodes for the CFTR chloride channel in epithelial cells, resulting in absent or significantly reduced chloride secretion of CFTR-expressing epithelia (1). Login to comment 5 ABCC7 p.Leu997Phe This genetic counseling included extended CFTR mutation screening (52 mutations, ethnically adapted: exon 2, 4, 7, 10, 11, 12, 13, 14b, 17a þ b, 21, intron 8 þ 19) and revealed heterozygosity for the L997F mutation in both parents and the fetus of the mother`s first pregnancy (who postnatally developed normally) (Fig. 1a). Login to comment 7 ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe Focusing on the previous results, both direct cycle sequencing of exon 17a and polymerase chain reaction (PCR) with sequence-specific primers for L997F were performed on the fetus` sample, revealing the first case of homozygosity for L997F (Fig. 1b). Login to comment 16 ABCC7 p.Leu997Phe Homozygosity for L997F was again confirmed, no other variants were detected, and the intron 8 status was determined to be IVS-8 T9/T9, TG10/TG10. Login to comment 17 ABCC7 p.Leu997Phe Further genetic analysis (sequence-specific PCR) of other members of this Turkish family (without proven CF individual) exhibited heterozygosity for L997F in both the paternal niece and additional relatives Clin Genet 2005: 67: 529-531 Copyright # Blackwell Munksgaard 2005 Printed in Singapore. Login to comment 22 ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe L997F has been shown to be a missense substitution with a change from leucine to phenylalanine at position 997, resulting from a G/C transition at position 3123 in exon 17a of the CFTR gene (2). Login to comment 24 ABCC7 p.Leu997Phe Both heterozygosity for L997F and compound heterozygosity with other CFTR mutations have been described in patients with disseminated bronchiectasis (9), recurrent idiopathic pancreatitis (10 - 12), sarcoidosis (13), primary sclerosing cholangitis (14), and newborns with hypertrypsinemia (10, 15). Login to comment 25 ABCC7 p.Leu997Phe Gomez Lira et al. (10) concluded to designate L997F as a CF-causing mutation after negative analysis of 100 Italian carriers of the F508del mutation (mothers of CF patients with typical symptomatology). Login to comment 26 ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe Our current clinical and laboratory evaluation of the first L997F homozygous individual strongly suggests that L997F is not a CF disease-causing mutation. Login to comment 28 ABCC7 p.Arg117His ABCC7 p.Leu997Phe We currently do not see evidence for the possibility of L997F being a 'mild` CFTR gene mutation (like R117H or 5T), resulting in CF disease only when found in compound heterozygosity with a 'severe` mutation. Login to comment 36 ABCC7 p.Leu997Phe Pedigree of the first L997F homozygous individual. Login to comment 39 ABCC7 p.Leu997Phe ABCC7 p.Leu997Phe Black ¼ L997F, gray ¼ no L997F, and white ¼ not examined for CFTR mutations. Login to comment 62 ABCC7 p.Leu997Phe Gomez Lira M, Benetazzo MG, Marzari MG et al. High frequency of cystic fibrosis transmembrane regulator mutation L997F in patients with recurrent idiopathic pancreatitis and in newborns with hypertrypsinemia. Login to comment