ABCMdb

PMID: 20880762

de Prada Merino A, Butschi FN, Bouchardy I, Beckmann JS, Morris MA, Hafen GM, Fellmann F
[R74W;R1070W;D1270N]: a new complex allele responsible for cystic fibrosis.
J Cyst Fibros. 2010 Dec;9(6):447-9. Epub 2010 Sep 28., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Arg74Trp Short Communication [R74W;R1070W;D1270N]: A new complex allele responsible for cystic fibrosis Ana de Prada Merinoa , Florence Niel Bütschia , Isabelle Bouchardyb , Jacques S. Beckmanna,c , Michael A. Morrisb , Gaudenz M. Hafend , Florence Fellmanna,⁎ a Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland b Service of Genetic Medicine, CMU, Geneva University Hospitals, Geneva, Switzerland c Department of Medical Genetics, University of Lausanne, 1011 Lausanne, Switzerland d Department of Paediatrics, Division of Respiratory Medicine, University Hospital of Lausanne, Switzerland Received 4 August 2010; accepted 19 August 2010 Available online 28 September 2010 Abstract Since the beginning of population screening for CF carriers, it has become apparent that complex CFTR alleles are not uncommon. Login to comment 5 ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp ABCC7 p.Arg1070Trp Keywords: Complex allele; R74W; D1270N; R1070W; CFTR; Cystic fibrosis 1. Login to comment 9 ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp Since the beginning of population screening for CF carriers, it has become apparent that complex alleles such as [R74W; D1270N] (HGVS nomenclature: c. Login to comment 12 ABCC7 p.Arg74Trp We report the observation of a new complex allele [R74W;R1070W;D1270N] associated with cystic fibrosis in a patient from a Moroccan family. Login to comment 43 ABCC7 p.Arg74Trp Segregation analysis showed the father to be a carrier of 711+1GNT, and the mother of a complex allele [R74W;R1070W;D1270N] (HGVS: c. Login to comment 46 ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp Discussion Here we report a new complex allele [R74W;R1070W; D1270N] in trans with a type I CFTR mutation in a patient with clinical diagnosis of CF and elevated sweat conductivity measurements. Login to comment 55 ABCC7 p.Arg74Trp The double mutant allele [R74W;D1270N], first described in 1995, was originally thought to be deleterious, although considered as a "mild" CFTR mutation responsible for a congenital bilateral absence of the vas deferens (CBAVD) phenotype [7,13]. Login to comment 57 ABCC7 p.Arg74Trp The same authors described the triple mutant [R74W;V201M;D1270N] associated with CBAVD when found in homozygous state or in trans with a severe CF mutation [14]. Login to comment 58 ABCC7 p.Arg74Trp ABCC7 p.Val201Met More recently, another group reported healthy male dizygotic twins carrying [R74W; V201M;D1270N] in trans with F508del, suggesting that this complex allele is not associated with classical CF [15]. Login to comment 59 ABCC7 p.Arg1070Trp To our knowledge, R1070W has never been described within a complex allele. Login to comment 60 ABCC7 p.Arg1070Trp ABCC7 p.Arg1070Trp R1070W is considered a mutation of "mild" pancreatic-sufficient CF or of CFTR-related disease including CBAVD [1,16]; functional studies have revealed abnormal localization of CFTR bearing R1070W [16]. Login to comment 98 ABCC7 p.Asp1270Asn ABCC7 p.Arg74Trp Are p.1148T, p.R74W and p.D1270N CF causing mutations? Login to comment 100 ABCC7 p.Arg74Trp [15] Brugnon F, Bilan F, Heraud MC, Grizard G, Janny L, Creveaux I. Outcome of intracytoplasmic sperm injection for a couple in which the man is carrier of CFTR p.[R74W;V201M;D1270N] and p.841R mutations and his spouse a heterozygous carrier of p.F508del mutation of CFTR gene. Login to comment