ABCMdb

PMID: 16283068

Chen HJ, Lin SP, Lee HC, Chen CP, Chiu NC, Hung HY, Chern SR, Chuang CK
Cystic fibrosis with homozygous R553X mutation in a Taiwanese child.
J Hum Genet. 2005;50(12):674-8. Epub 2005 Nov 10., [PubMed]

Sentences

No. Mutations Sentence Comment

13 ABCC7 p.Arg553* We report a 3-year-5-month-old boy born to Taiwanese parents with classical clinical manifestations of cystic fibrosis and who has a homozygous R553X mutation of the CFTR gene. Login to comment 62 ABCC7 p.Arg553* A homozygous R553X mutation was detected, which was also confirmed by direct sequencing of the polymerase chain reaction (PCR) product, using the technique described in our previous paper (Cheng et al. 2005). Login to comment 64 ABCC7 p.Arg553* His nonconsanguineous parents were subsequently both found to be R553X mutation carriers. Login to comment 65 ABCC7 p.Arg553* The biparental origins of the R553X mutation were determined by quantitative fluorescent PCR (QF-PCR) using short tandem repeat polymorphic DNA markers specific for both the short arm and long arm of chromosome 7 (Table 1). Login to comment 71 ABCC7 p.Arg553* The R553X mutation accounts for 1.1% of cystic fibrosis chromosomes in Caucasian populations (Cheadle et al. 1992a, b), but it has never before been reported in a Taiwanese patient. Login to comment 72 ABCC7 p.Arg553* Both parents of our patient were heterozygous for the R553X mutation. However, there was no known consanguinity within the parents` families. Login to comment 74 ABCC7 p.Arg553* It is interesting to speculate on the origin of the R553X mutation in this family, as it most likely came from Westerners. Login to comment 79 ABCC7 p.Arg553* The nonsense mutation R553X occurs in exon 11 of the CFTR gene and produces a truncated protein missing the regulatory domain, the second nucleotide binding fold, and the second transmembrane span, leading to a reduction or absence of cytoplasmic CFTR mRNA (Will et al. 1993). Login to comment 80 ABCC7 p.Arg553* Most Caucasian patients who have the R553X mutation are heterozygous for it. Login to comment 81 ABCC7 p.Arg553* Only two patients homozygous for R553X have been reported, one by Bal et al. (1991) and the other by Cheadle et al. (1992a, b). Login to comment 84 ABCC7 p.Arg553* Both of these individuals had a later age of onset and relatively mild pulmonary involvement compared with patients heterozygous for the R553X mutation. Login to comment 86 ABCC7 p.Arg553* This would explain the relatively mild clinical course in these two patients with a homozygous R553X mutation. However, our patient had Table 1 Genotypic information of the proband, his sister, and parents at short tandem repeat (STR) markers specific for chromosome 7 obtained by fluorescent polymerase chain reaction (PCR) assays. Login to comment