ABCMdb

PMID: 1281033

Harris A
Cystic fibrosis gene.
Br Med Bull. 1992 Oct;48(4):738-53., [PubMed]

Sentences

No. Mutations Sentence Comment

79 ABCC7 p.Gly551Asp Recent data on AF5O8 epithelial cells would support this.45 FIBROSIS 7 4 Other relatively frequent mutations in the first NBF include deletion of the isoleucine residue adjacent to F508 (AI507)38 - 38a {see Fig 4 in chapter by Super, this issue); substitution of the glycine at amino acid 551 by aspartic acid (G551D)39 ; 'stop' mutations at arginine 55339 and glycine M246 substitutions of serine 549 by various residues38 - 38a > 39 and a predicted splicing mutation at the start of exon 11 (1717-1 G->A).38 MUTATIONS IN THE REGULATORY DOMAIN The 723 bp exon 13, which codes for the R domain contains relatively few mutations compared to the rest of the CFTR cDNA and none of them are common. Login to comment 87 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys One of these is sufficiently common to warrant specific mention, it is a 'stop' mutation at amino acid 1282 (W1282X).46 Another common mutation in this region is found in exon 21, the substitution of aspargine 1303 by lysine (N1303K)/» IMPLICATIONS OF DISTRIBUTION OF MUTATIONS Clearly the analysis of mutations within CFTR has potential power in shedding light on functionally important regions of the CFTR protein. Login to comment 98 ABCC7 p.Gly542* ABCC7 p.Gly542* It has been reported that the G542X mutation when present in a homozygous form may lead to a milder form of CF than AF508 homozygotes or heterozygotes AF508/G542X.57 Similarly other patients with predicted 'stop' mutations in both CF genes may be less severely affected than AF508 homozygotes.58 In other words if the 'stop' mutation actually abolishes production of CFTR this may be less deleterious than having a malfunctioning protein such as the A508 protein. Login to comment 114 ABCC7 p.Gly551Ser In one case two siblings with mild pulmonary disease and normal sweat electrolyte concentrations were found to be homozygous for a glycine to serine substitution at amino acid 551 in the first NBF of CFTR.31 Other patients with this phenotype were found to carry a 750 CYSTIC FIBROSIS GENE mutation in intron 19 that caused the insertion of 83bp into the CFTR mRNA32 or to be compound heterozygotes for other denned mutations in CFTR.™ Another interesting phenotype that may be associated with mutations in CFTR is that of congenital absence of the vas deferens. Login to comment