ABCMdb

PMID: 12124743

Salvatore F, Scudiero O, Castaldo G
Genotype-phenotype correlation in cystic fibrosis: the role of modifier genes.
Am J Med Genet. 2002 Jul 22;111(1):88-95., 2002-07-22 [PubMed]

Sentences

No. Mutations Sentence Comment

18 ABCC7 p.Trp1282* ABCC7 p.Arg1162* ABCC7 p.Tyr122* ABCC7 p.Thr338Ile Several mutations are frequent in specific populations: W1282X among Ashkenazi [Shoshani et al., 1992], 2143delT in Germany [Dork et al., 1994], Y122X in Iceland [Chevalier-Porst et al., 1994], T338I in Sardinia, and 2183AA > G and R1162X in Northeast Italy [Rendine et al., 1997]. Login to comment 25 ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly542* Several mutations of this group have a frequency of > 2% among CF chromosomes within most populations studied, e.g., W1282X [Shoshani et al., 1992], R553X, and G542X [Casals et al., 1993]. Login to comment 28 ABCC7 p.Gly551Asp Class 3 mutations affect the regulatory domains of the CFTR protein and include G551D, which is frequent in Northern Europe. Login to comment 46 ABCC7 p.Arg117His ABCC7 p.Pro574His ABCC7 p.Ala455Glu ABCC7 p.Gly1349Asp ABCC7 p.Arg334Trp ABCC7 p.Arg347Pro ABCC7 p.Arg347His ABCC7 p.Arg347Leu ABCC7 p.Ser1251Asn ABCC7 p.Arg352Gln ABCC7 p.Pro205Ser ABCC7 p.Gly85Glu ABCC7 p.Ser549Asn ABCC7 p.Thr338Ile ABCC7 p.Asp1152His ABCC7 p.His1085Arg ABCC7 p.Phe1052Val ABCC7 p.Gly91Arg ABCC7 p.Arg1066His ABCC7 p.Ser492Phe ABCC7 p.Glu193Lys ABCC7 p.Cys866Tyr ABCC7 p.Asp579Gly ABCC7 p.His1054Asp ABCC7 p.Phe1286Ser ABCC7 p.Ser1159Pro A series of mutations usually associated with pancreatic sufficiency have been identified and defined as ''mild`` with reference to pancreatic status [Kerem et al., 1989c]: G85E, G91R, R117H, E193K, P205S, R334W, T338I, R347H, R347L, R347P, R352Q, A455E, S492F, S549N, P574H, D579G, 711 þ 5 G > A, C866Y, F1052V, H1054D, R1066H, R1068H, H1085R, D1152H, S1159P, S1251N, F1286S, G1349D, 2789 þ 5 G > A, and 3849 þ 10kb C > T [Dean et al., 1990; Cutting et al., 1990a; Cremonesi et al., 1992; Highsmith et al., 1994]. Login to comment 59 ABCC7 p.Arg117His ABCC7 p.Ala455Glu Several findings suggest that the pulmonary phenotype is directly related to the CFTR genotype: 1) missense mutations (e.g., R117H and A455E) give rise to a milder pulmonary expression [Gan et al., 1995; De Braekeleer et al., 1997]; 2) CF patient homozygotes for DF508 and compound heterozygotes for DF508 and a nonsense mutation at the level of the nucleotide binding folder (NBF) encoding region of the CFTR gene are more susceptible to P. aeruginosa infections [Kubesch et al., 1993; Davidson et al., 1995]; and 3) CF patient homozygotes for DF508 invariably have a severe pulmonary phenotype [Johansen et al., 1991]. Login to comment 65 ABCC7 p.Arg553* ABCC7 p.Gly542* Secondly, pulmonary expression was heterogeneous in CF patient homozygotes for nonsense mutations, although CFTR mRNA was not detected at the pulmonary level in these patients [Hamosh et al., 1991]; for example, a mild pulmonary expression has been reported in several patient homozygotes for nonsense mutations [Cutting et al., 1990b; Cuppens et al., 1990], such as R553X [Castaldo et al., 1996] and G542X [Castaldo et al., 1997]. Login to comment 66 ABCC7 p.Trp1282* ABCC7 p.Arg1158* ABCC7 p.Arg1158* On the contrary, a severe pulmonary phenotype was reported in 16 CF patient homozygotes for W1282X [Shoshani et al., 1992], and more recently in the first CF patient homozygote for the R1158X nonsense mutation [Castaldo et al., 1999], while a double heterozygote for R1158X showed a mild phenotype [Frossard et al., 2000]. Login to comment 87 ABCC7 p.Gly542* Similarly, we described a CF patient homozygous for the G542X mutation who had a very severe liver phenotype, unlike the six previously reported cases with this CFTR genotype, who were free of liver involvement [Castaldo et al., 1997]. Login to comment 97 ABCC7 p.Gly551Asp After gene cloning, Hamosh et al. [1992] found that G551D carried a decreased risk of meconium ileus in contrast to previous studies [Kerem et al., 1989c]. Login to comment