ABCMdb

PMID: 7683954

Nunes V, Chillon M, Dork T, Tummler B, Casals T, Estivill X
A new missense mutation (E92K) in the first transmembrane domain of the CFTR gene causes a benign cystic fibrosis phenotype.
Hum Mol Genet. 1993 Jan;2(1):79-80., [PubMed]

Sentences

No. Mutations Sentence Comment

1 ABCC7 p.Glu92Lys 79-80 A new missense mutation (E92K) in the first transmembrane domain of the CFTR gene causes a benign cystic fibrosis phenotype V.Nunes, M.Chill6n, T.Dfirk1 , B.Tummler1 , T.Casals and X.Estivill* Molecular Genetics Department, Cancer Research Institute (IRO), Hospital Duran i Reynals, Campus Bellvitge, Av. Castelldefels Km 2.7, L'Hospitalet de LJobregat, E-08907 Barcelona, Spain and 1 Abteilung Biophysikalische Chemie, OE 4350, Medizinische Hochschule Hannover, D-30XX) Hannover 61, Germany Received October 22, 1992; Revised and Accepted October 30, 1992 The Cystic Fibrosis Transmembrane Conductance (CFTR) gene contains 27 exons spread over approximately 250 kb of genomic DNA (1,2,3). Login to comment 3 ABCC7 p.Glu92Lys We describe a new missense mutation in exon 4 of the CFTR gene, E92K, discovered by single strand conformation polymorphism (SSCP) (5) analysis, in the screening of Spanish CF families. Login to comment 4 ABCC7 p.Glu92Lys ABCC7 p.Glu92Lys The clinical features of a heterozygous E92K/unknown mutation and an E92K homozygous patient are described. Login to comment 8 ABCC7 p.Arg117His ABCC7 p.Asp110His SSCP conditions for exon 4 of the CFTR gene, which allow discrimination of mutant and wild type alleles, were developed for several control mutations at this exon: D110H, R117H, 556delA and 621+ 1G-T (8, 9). Login to comment 10 ABCC7 p.Glu92Lys ABCC7 p.Glu92Lys Analysis of the abnormal band showed that it contained a G to A transition (G-A at 406) that replaces glutamic acid by lysine at codon 92 of exon 4 (mutation E92K) (Figure IB). Login to comment 11 ABCC7 p.Glu92Lys E92K can easily be detected by restriction enzyme digestion, as the mutation destroys an EcoNl site. Login to comment 15 ABCC7 p.Glu92Lys The subsequent screening of German patients for mutations in exon 4, including E92K, led to the identification of a homozygous patient for this mutation. Login to comment 17 ABCC7 p.Glu92Lys E92K was not detected in further 150 non-AF508 German CF chromosomes. Login to comment 18 ABCC7 p.Glu92Lys Clinical characteristics of the two patients carrying mutation E92K are shown in Table 1. Login to comment 19 ABCC7 p.Glu92Lys The two affected boys are of similar 10 11 12 13 14 15 16 17 18 19 B Normal Heterozygous 1 ' • * A 1 1 \ 1 N A A • Cut fragment L A A A • EXON 4 E92K Figure 1. Login to comment 20 ABCC7 p.Glu92Lys Characterization of mutation E92K. Login to comment 26 ABCC7 p.Arg117His Lanes 1 and 2 were R117H and621 + l G - T mutations used as controls. Login to comment 27 ABCC7 p.Glu92Lys The abnormal fragment corresponding to mutation E92K is in lane 18. Login to comment 32 ABCC7 p.Glu92Lys Clinical and laboratory features of E92K individuals Genotype Current age Age at diagnosis Sex Sweat chloride mEq./l. Login to comment 33 ABCC7 p.Glu92Lys Meconium ileus Dehydration Height-cm (%ile) Weight-Kg (%ile) Chrispin - Norman* Lung colonization with bacterial pathogens Pancreatic insufficiency Shwachman - Kulczyclrib FEV1-% predicted FVC-% predicted Other clinical features Patient Spanish E92K/unknown 9 y. Login to comment 34 ABCC7 p.Glu92Lys ABCC7 p.Glu92Lys 6 m. 9 months male 92 no no 135(75) 27 (45) 1 no no 100 98 88 no Turkish E92K/E92K 8 y. Login to comment 44 ABCC7 p.Glu92Lys E92K is a missense mutation in the first nucleotide of exon 4, occurring in the first transmembrane domain of the CFTR gene. Login to comment 48 ABCC7 p.Glu92Lys As both E92K chromosomes are associated with the same 2-2-1-1-1 haplotype for MetH/MspI, XV-2c/TaqI, KM.19/PstI, MP6d-9/MspI, J3.11/Mspl, a common origin of this mutation could be postulated, which should be further confirmed using intragenic markers (12). Login to comment 49 ABCC7 p.Glu92Lys It might be useful to consider mutation E92K when analysing CF chromosomes from Northern African and Anatolian or Iranian/Armenian CF chromosomes. Login to comment 50 ABCC7 p.Glu92Lys The E92K homozygous patient has allowed us to assess clinical features for this mutation alone, establishing a good correlation between the mutation and the benign phenotype produced. Login to comment 51 ABCC7 p.Glu92Lys The other E92K patient, who has an as yet uncharacterized mutation in the other CF chromosome, also has a very moderate presentation. Login to comment 52 ABCC7 p.Glu92Lys Therefore, clinical data in both patients suggest that E92K is a very benign CF mutation, accompanied by the absence of classical CF symptoms of pulmonary and gastrointestinal disease. Login to comment