ABCMdb

PMID: 24225052

Parisi GF, Cutello S, Di Dio G, Rotolo N, La Rosa M, Leonardi S
Phenotypic expression of the p.Leu1077Pro CFTR mutation in Sicilian cystic fibrosis patients.
BMC Res Notes. 2013 Nov 13;6:461. doi: 10.1186/1756-0500-6-461., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Leu1077Pro ABCC7 p.Leu1077Pro ABCC7 p.Leu1077Pro SHORT REPORT Open Access Phenotypic expression of the p.Leu1077Pro CFTR mutation in Sicilian cystic fibrosis patients Giuseppe Fabio Parisi, Silvia Cutello, Giovanna Di Dio, Novella Rotolo, Mario La Rosa and Salvatore Leonardi* Abstract Background: The p.Leu1077Pro CFTR mutation was firstly described in 1992 as a mild allele that confers a pancreatic sufficiency phenotype but the information collected in database CFTR2 lead to consider p.Leu1077Pro as a severe CF mutation. Login to comment 1 ABCC7 p.Leu1077Pro Although it is typical of Southern Italy, p.Leu1077Pro is not included in the mutation panel firstly tested in individuals originated from this area. Login to comment 4 ABCC7 p.Leu1077Pro 4 patients who were heterozygous for the p.Leu1077Pro mutation were included in the study. Login to comment 5 ABCC7 p.Leu1077Pro In our Cystic Fibrosis Centre, the prevalence of p.Leu1077Pro is 3.6% among all mutations. All patients had positive sweat test values, pancreatic insufficiency and pulmonary exacerbations. Login to comment 7 ABCC7 p.Leu1077Pro Conclusions: We found that the p.Leu1077Pro CFTR mutation is associated with a classic CF phenotype confirming what is reported in CFTR2 database. Login to comment 8 ABCC7 p.Leu1077Pro The relatively high prevalence of p.Leu1077Pro associated with the severe clinical course of the disease in patients bearing this mutation is of interest for genetic counselling purposes, as it should be part of mutation panel to be tested in individuals originated from Southern Italy. Login to comment 9 ABCC7 p.Leu1077Pro Keywords: Cystic fibrosis, CFTR, pLeu1077Pro, L1077P, Genotype-phenotype, Sicilian patients Background Cystic fibrosis (CF) is the most common life-shortening monogenic genetic disease in Caucasians. Login to comment 17 ABCC7 p.Leu1077Pro ABCC7 p.Leu1077Pro The p.Leu1077Pro (L1077P) mutation consists in a transition T to C at nucleotide position 3362 in exon 17b of CFTR cDNA that is responsible of change of Leucine (CTG) to Proline (CCG) at position 1077 of the protein. This mutation belongs to the class III CFTR mutations and produce a protein that is trafficked to the cell membrane but does not respond to cAMP stimulation [8]. Login to comment 22 ABCC7 p.Leu1077Pro [8] firstly found evidence that the p.Leu1077Pro was associated with a pancreatic sufficiency even if their study did not contain functional data. Login to comment 23 ABCC7 p.Leu1077Pro The information collected in database CFTR2 [9], analyzing data from 40 patients with this mutation, lead to consider p.Leu1077Pro as a severe CF mutation, associated with PI in 78% of patients and Pseudomonas Aeruginosa infection in 55% of patients. Login to comment 25 ABCC7 p.Leu1077Pro [10] and although it should be predictive of a severe CF phenotype, p.Leu1077Pro is not included in the mutation panel firstly tested in individuals originated from this area since the information collected in CFTR2 are only available from 2011, and the only information held prior to the creation of this database were related to the work of Bozon et al. Login to comment 26 ABCC7 p.Leu1077Pro The aim of our study was therefore to describe prevalence and clinical features in Sicilian patients bearing the p.Leu1077Pro CFTR mutation followed in our Cystic Fibrosis Centre to add new data on this issue. Login to comment 30 ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Leu1077Pro Four patients (3 males, age range 7 - 20 years) who were heterozygous for the p.Leu1077Pro mutation were included in the study: three patients also carried the p.Phe508del (ƊF508) mutation in the second allele while one carried the p.Asn1303Lys (N1303K) mutation. Login to comment 49 ABCC7 p.Asn1303Lys ABCC7 p.Leu1077Pro ABCC7 p.Leu1077Pro ABCC7 p.Leu1077Pro ABCC7 p.Leu1077Pro Table 1 Demographic data of the patients Patient Sex Age BMI Age of diagnosis Genotype Sweat chloride (mmol/L) IRT (ng/ml) 1 M 7 yrs 14.57 (Underweight) Birth p.Phe508del/p.Leu1077Pro 112 84/43 2 M 10 19.80 (Normal weight) Birth p.Phe508del/p.Leu1077Pro 101 155/215 3 M 12 19.63 (Normal weight) Birth p.Phe508del/p.Leu1077Pro 97 181/100 4 F 20 16.44 (Underweight) 4 months p.Asn1303Lys/p.Leu1077Pro 108 NA BMI: body mass index. Login to comment 59 ABCC7 p.Leu1077Pro The p.Leu1077Pro mutation was identified by denaturing high-performance liquid chromatography (d-HPLC) and confirmed by gene sequencing analysis with an automated procedure (Genetic Analyzer, Applied Biosystems). Login to comment 61 ABCC7 p.Leu1077Pro Results In our Eastern Sicilian Cystic Fibrosis Centre, the prevalence of p.Leu1077Pro is 3.6% among all mutations. All patients had pancreatic insufficiency treated with enzyme replacement therapy. Login to comment 72 ABCC7 p.Leu1077Pro Discussion The present study provides evidence that the p.Leu1077Pro is a relatively frequent mutation associated with a phenotype characterized by pathological sweat test, pancreatic insufficiency and pulmonary disease. Login to comment 73 ABCC7 p.Leu1077Pro The p.Leu1077Pro mutation consists in a transition T to C at nucleotide position 3362 in exon 17b of CFTR cDNA that is responsible of change of Leucine (CTG) to Proline (CCG) at position 1077 of the protein. This mutation belongs to the III class CFTR mutations and produce a protein that is trafficked to the cell membrane but does not respond to cAMP stimulation [8]. Login to comment 76 ABCC7 p.Leu1077Pro Nevertheless p.Leu1077Pro mutation, although belonging to the class III CFTR mutations, was classified by Bozon et al. Login to comment 83 ABCC7 p.Leu1077Pro On this regard, the mutation p.Leu1077Pro is typical of Southern Italy, overall in Puglia, in which the prevalence is higher (1.9% among all mutations) than in the world (< 1%) [10]. Login to comment 89 ABCC7 p.Leu1077Pro All of them had a p.Phe508del/p.Leu1077Pro genotype. Login to comment 91 ABCC7 p.Asn1303Lys ABCC7 p.Leu1077Pro She had a p.Asn1303Lys/p.Leu1077Pro genotype. Login to comment 100 ABCC7 p.Asn1303Lys However, given the association with a severe mutation such as p.Phe508del and p.Asn1303Lys, it is clear that only a follow-up could allow definitive conclusions on the course of the pulmonary disease in patients with this genotype/ phenotype profile. Login to comment 101 ABCC7 p.Leu1077Pro The relatively high prevalence of p.Leu1077Pro associated with the severe clinical course of the disease in patients bearing this mutation is of interest for genetic counselling purposes, as it should be part of mutation panel to be tested in individuals originated from Southern Italy. Login to comment 132 ABCC7 p.Ile148Thr ABCC7 p.Tyr1092* ABCC7 p.Leu1077Pro Bozon D, Zielenski J, Rininsland F, Tsui LC: Identification of Four New Mutation in the Cystic Fibrosis Transmembrane Conductance Regulator Gene: I148T, L1077P, Y1092X, 2183AA ࢐ G. Login to comment 176 ABCC7 p.Leu1077Pro : Phenotypic expression of the p.Leu1077Pro CFTR mutation in Sicilian cystic fibrosis patients. Login to comment