ABCMdb

PMID: 15482777

Wong LJ, Alper OM, Hsu E, Woo MS, Margetis MF
The necessity of complete CFTR mutational analysis of an infertile couple before in vitro fertilization.
Fertil Steril. 2004 Oct;82(4):947-9., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCC7 p.Arg553* Result(s): The child with classic CF had ⌬F508 and R553X mutations. Login to comment 6 ABCC7 p.Arg117Cys Two children with mild CF symptoms had ⌬F508 and R117C. Login to comment 7 ABCC7 p.Arg553* ABCC7 p.Arg117Cys The father carried two mutations, R553X and R117C. Login to comment 14 ABCC7 p.Arg117Cys Key Words: Cystic fibrosis, CFTR, R117C, triplet CF, IVF, infertility Cystic fibrosis (CF) is the most common, life-shortening autosomal recessive disease in whites with extreme morbidity and mortality. Login to comment 48 ABCC7 p.Arg553* The results of molecular analysis revealed that the mother was heterozygous for ⌬F508 and the father was heterozygous for R553X. Login to comment 53 ABCC7 p.Arg553* DNA analysis of patient 1 revealed a compound heterozygote of ⌬F508/R553X, confirming the diagnosis of CF. Login to comment 67 ABCC7 p.Arg117Cys A rare mutation, R117C, was identified. Login to comment 69 ABCC7 p.Arg553* ABCC7 p.Arg117Cys ABCC7 p.Arg117Cys Triplet 1 2 3 Age at diagnosis At birth 2 month 3 year Genotype ⌬F508/R553X ⌬F508/R117C ⌬F508/R117C Sex M M F Sweat chloride (mEq/L) 98 48 67 Pancreatic function PI PS PS Enzyme supplement Pancreacarb MS8 None None Microbial colonization n/a n/a n/a Height/weight (at 3,4,4 years of age) 92.7 cm (Ͻ5%) 97 cm (5%) 98 cm (25%) 12.7 kg (Ͻ5%) 13.4 kg (10%) 13.8 kg (10%) Complications Biliary atresia Developmental delay DIOS Allergic rhinitis Hearing loss RAD Hypospadia Allergic rhinitis UAVD Allergic rhinitis Meconium ileus Yes No No Note: PI ϭ pancreatic insufficiency as determined by the patient`s dependence on pancreatic enzyme supplements; PS ϭ pancreatic sufficiency; UAVD ϭ unilateral absence of vas deferens; DIOS ϭ distal intestinal obstruction syndrome; RAD ϭ reactive airways disease; n/a ϭ not available. Login to comment 76 ABCC7 p.Arg553* ABCC7 p.Arg117Cys ABCC7 p.Arg117Cys Subsequent genotyping of the family members revealed a compound heterozygote of ⌬F508/R117C in patient 2, and a compound heterozygote of R553X/R117C in the father. Login to comment 78 ABCC7 p.Arg553* DISCUSSION The truncation mutation R553X in exon 11, which results in the loss of part of the first ATP binding site, the regulatory R domain, the second transmembrane spanning region, and the second ATP binding site, in combination with ⌬F508 on the other allele in patient 1, is consistent with a classic CF phenotype (9). Login to comment 79 ABCC7 p.Arg117Cys The R117C is a rare mutation with a frequency of about 0.2% in the US white CF population (10). Login to comment 80 ABCC7 p.Arg117His The more common mutation affecting the same amino acid is R117H, about 0.7% in the US white CF population (10), which is located at the external end of the second transmembrane domain of the CFTR protein (9). Login to comment 81 ABCC7 p.Arg117His The partial penetrance of R117H mutation depends on the cis-located 5T tract in intron 8 and possibly also by nuclear modifier genes (7, 11-13). Login to comment 85 ABCC7 p.Arg117His The substitution of the basic amino acid arginine with another basic amino acid histidine is predicted to be mild, as it has been observed in patients with the R117H mutation. Login to comment