ABCMdb

PMID: 7505690

Ferec C, Verlingue C, Guillermit H, Quere I, Raguenes O, Feigelson J, Audrezet MP, Moullier P, Mercier B
Genotype analysis of adult cystic fibrosis patients.
Hum Mol Genet. 1993 Oct;2(10):1557-60., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCC7 p.Gly542* All these patients are compound heterozygote, seven carrying the AF508 and one the G542X on one allele. Login to comment 5 ABCC7 p.Arg117His ABCC7 p.Arg334Trp ABCC7 p.Ile336Lys ABCC7 p.His1054Asp The other allele carried is: (i) a missense mutation located in exons coding for transmembrane region in five patients [R334W (1); I336K (2); R117H (1); H1054D (1)]; (ii) a splice mutation in two patients [2789 + 5G - A], (ill) an uncharacterised mutations In one patient. Login to comment 32 ABCC7 p.His1054Asp However the Histidine being replaced by an Aspartic Acid at codon 1054 (H1054D) of exon 17b is a novel amino acid change previously undescribed (figure 1). Login to comment 34 ABCC7 p.His1054Asp Also, this particular amino acid is * To whom correspondence should be addressed atUniversityofNorthCarolinaatChapelHillonOctober25,2012http://hmg.oxfordjournals.org/Downloadedfrom conserved through evolution and the replacement has not been observed on more than 200 normal chromosomes Amplification of exon 17b, followed by digestion with Sau 3AI, allows a rapid screening for H1054D, whereby the mutation creates a restriction site for Sau3AI. Login to comment 35 ABCC7 p.Arg334Trp R334W corresponds to the replacement of an Arginine by a Tryptophan, at position 334 in exon 7 which encodes part of the first transmembrane domain of the CFTR molecule is a missence mutation which has been reported by Kristidis et al. to be associated with PS (17). Login to comment 36 ABCC7 p.Ile336Lys The I336K which results in a Lysine instead of an Isoleucine (Cassiman, personal communication), is found in two patients Figure 1. Login to comment 37 ABCC7 p.His1054Asp Sequencing data of the H1054D mutation. Login to comment 40 ABCC7 p.Ile336Lys The I336K, introduces an Sspl restriction site in exon 7 and can, therefore, be detected by digestion with this enzyme. Login to comment 41 ABCC7 p.Arg117His The R117H exchanges an Arginine for an Histidine and is a missense mutation in exon 4 coding for a transmembrane domain (18). Login to comment 57 ABCC7 p.Arg117His ABCC7 p.Gly542* ABCC7 p.Ile336Lys '*'* < GENOTYPE * • • ;i^>"; ' ' FUJ34W/G542X Exon 7/ Exon 11 Arginine •-> Tryptophan AF508/I336K Exon 10/Exon 7 Isoleucine ••> Lysine AF5O8/H1054O Exon 10/Exon 17b Histidine --> Aspartc Acid AF508 Unknown AF508 / 2789+5 G->A Exon 10/ Exon 14b Splice mutation AF508/2789+5 G->A Exon 10/ Exon 14b Splice mutation AF5O8/R117H Exon 10/Exon 4 Arginine -->Histidine AF508/O36K Exon 10/Exon 7 Isoteucine ••> Lysine SEX 4 M F M M F F F M DIAGNOSiS 13 13 27 17 39 32 30 17 PROFESSIONAL; . Login to comment 72 ABCC7 p.His1054Asp In this paper, we report the determination of the genotype of 7 out of 8 adult CF patients and of one possible novel allele H1054D. Login to comment 74 ABCC7 p.His939Asp Such an amino acid change i.e. aspartic acid for histidine has been observed elsewhere in the CFTR gene, for example H939D (CF Consortium, personal communication) and considered also as a possible CF allele. Login to comment 85 ABCC7 p.Arg117His One patient (7) (genotype AF508/R117H) has a deteriorated pulmonary function. As these diagnostic tests are being carried out for these patients of mature years (30 years), of whom many were previously misdiagnesed previously, and as a result given inappropriate treatment, this may account for degeneration of their pulmonary functions. Login to comment 87 ABCC7 p.Ile336Lys In this group two patients (a brother and a sister) compound heterozygotes for AF5O8 and I336K present with different phenotypes with regard to pancreatic status and pulmonary function, the male being PS and free of Pseudomonas Aeruginosa colonisation at 40 years old. Login to comment 91 ABCC7 p.Arg334Trp ABCC7 p.Ile336Lys ABCC7 p.His1054Asp Several different types of mutations have been found in this group, a splice mutation being present in two patients (2789+5 G - A in exon 14b), and missense mutations (R334W in exon 7, I336K in exon 7, Rl 17H in exon 4 and H1054D in exon 17b) present in the others. Login to comment 92 ABCC7 p.Arg117His The mutation R117H has been found to be associated with congenital bilateral absence of vas deferens (30) which is now considered as a genital phenotype of CF (31). Login to comment 93 ABCC7 p.Arg117His However it is interesting to note that we described in this paper a fertile female bearing a DF508/R117H genotype. Login to comment 98 ABCC7 p.Arg117His ABCC7 p.Arg334Trp Recently Sheppard et al. (33) have shown that CFTR carrying either R117H or R334W are correctly processed and when expressed in heterologous cells are able to generate cyclic AMP regulated Cl~ current, although at a much lower level. Login to comment