ABCMdb

PMID: 9709387

Wilschanski M, Durie PR
Pathology of pancreatic and intestinal disorders in cystic fibrosis.
J R Soc Med. 1998;91 Suppl 34:40-9., [PubMed]

Sentences

No. Mutations Sentence Comment

84 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* The next most common mutations are G542X, G551D, N1303K and W1282X, each of which account for 1% to 2.5% of CF chromosomes throughout the world. Login to comment 85 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Two are missense mutations (G55 ID, N1303K) resulting in an amino acid substitution of the protein product, while G542X and W1 282X are nonsense mutations which give rise to a premature stop codon, leading to the expression of no CFTR or a non-functional truncated protein. Login to comment 88 ABCC7 p.Trp1282* For example, the stop mutation W1282X is present on approximately 50% of Ashkenazi Jewish chromosomes, making it the most common mutation in this particular population. Login to comment 97 ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Gly542* Molecular consequences of cftr gene mutations Several classification systems have been developed in an attempt to define the large number of cftr gene mutations on 43 I =ON 4o0 o 00 4O0 40 40 I II 111 IV V Normal NOmAfl Missnso G542X Missmnse Missense Missense A455E Fremeshift AA dIeIIOn 05510 R117H Allerndve 39soTT AF508 spiRlng Spl$oeJunculon 3849t10kbC4T1717-1G-4A Figure 4 Molecular consequences of cystic fibrosis transmembrane conductance regulator mutations. Login to comment 114 ABCC7 p.Gly551Asp G551D is an example of a class III mutation. Login to comment 117 ABCC7 p.Arg117His Class IV mutations produce protein that reaches the apical membrane, are capable of generating a cAMP regulated apical membrane chloride current, but have altered ionic properties resulting in a reduction in the amount of current; an example is the R117H mutation. Login to comment 119 ABCC7 p.Ala455Glu Class V mutations result in reduced synthesis of normal functioning CFTR due to defective processing (A455E) or aberrant splicing at alternative sites (3849+10kbC-T). Login to comment 152 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Pro574His ABCC7 p.Ala455Glu ABCC7 p.Trp1282* ABCC7 p.Gly551Ser ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Arg352Gln ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Arg560Thr ABCC7 p.Gly480Cys A small number of more Table 1 Classification of cystic fibrosis gene mutation as severe, mild or indeterminate with respect to pancreatic function Severe Mild Variable (classes 1, I/ or 111) (classes IV or V) (classes IV or V) AF508 R117H G85E 1148T R334W 2789+5G-*A G480C R347P G551D A455E R560T P574H N1303K 3849+1 Okb C-+T G542X G551S W1282X P5748 621 +1 G-T R352Q 1717-1G-T T3381 556delA Adapted from Ref 20 with permission recently described mutations [G85E and 278+5G-÷AI are less clearly determinant with respect to the pancreatic sufficient and pancreatic insufficient phenotypes. Login to comment 168 ABCC7 p.Gly542* An early study suggested that the nonsense mutation G542X is associated with an increased risk of meconium ileus, but this association has not been confirmed in a study of larger patient cohort. Login to comment 169 ABCC7 p.Gly551Asp The CF genotype-phenotype consortium has reported a lower incidence of meconium ileus among compound heterozygotes carrying G551D/JIF508 (6.4%) in comparison with 19.5% in patients homozygous for JF50824. Login to comment