ABCMdb

PMID: 10836331

Frossard PM, Hertecant J, Bossaert Y, Dawson KP
Genotype-phenotype correlations in cystic fibrosis: clinical severity of mutation S549R(T-->G).
Eur Respir J. 1999 Jan;13(1):100-2., [PubMed]

Sentences

No. Mutations Sentence Comment

21 ABCC7 p.Ser549Arg In this report, the clinical characteristics that are associated with this mutation in a group of 15 CF patients who are homozygous for S549R are presented. Login to comment 38 ABCC7 p.Ser549Arg CFTR S549R mutation analysis Deoxyribonucleic acid (DNA) was extracted from leukocytes isolated from 2±5 mL of the subject's venous blood collected in ethylenediaminetetraacetic acid (EDTA) tubes according to standard protocols [17]. Login to comment 39 ABCC7 p.Ser549Arg The detection of mutation S549R localized in exon 11 (T?G at nucleotide 1779) was performed routinely by DraIII restriction endonuclease analysis of exon 11 polymerase chain reaction (PCR) products, and the mutation was confirmed by sequencing analysis according to protocols and conditions that have been described elsewhere [14]. Login to comment 40 ABCC7 p.Ser549Arg Results The clinical presentation of 15 CF children (6 males and 9 females) who were homozygous for mutation S549R wasdetermined.Theclinicaldescriptionofthepooledgroup of patients is presented in table 1. Login to comment 49 ABCC7 p.Ser549Arg Discussion S549R is a missense mutation that was first reported in 1989 by KEREM et al. Login to comment 50 ABCC7 p.Ser549Arg [18] in a Moroccan Jewish individual who was a compound heterozygote S549R/DF508. Login to comment 53 ABCC7 p.Ser549Arg [19] screened 105 mutations in 600 CF patients from France and identified one S549R homozygote. Login to comment 57 ABCC7 p.Arg117His [20] showed that a close association exists between chromosome background of the R117H mutation and clinical phenotype, which means that the genetic context in which a mutation occurs can play a significant role in determining the type of illness produced. Login to comment 63 ABCC7 p.Ser549Arg Previous work [14] by the authors indicated that all CF patients of Bedouin origin that have been investigated so far were homozygous for S549R (T?G), which led to the hypothesis that the mutation is the result of a founder effect that occurred in an ancestral Bedouin tribe. Login to comment 64 ABCC7 p.Ser549Arg ABCC7 p.Ser549Arg Although S549R has been described elsewhere as a private mutation only, the uniquely high number of homozygotes in the UAE allowed us to evaluate the overall clinical presentation that is associated with S549R. Login to comment 65 ABCC7 p.Ser549Arg This data indicates that S549R is a very severe mutational allele. Login to comment 70 ABCC7 p.Ser549Arg Sweat chloride concentrations associated with S549R homozygosity were high, even at very young ages (mean sweat chloride levels in the group of 15 patients were 12021 mEq.L-1 ). Login to comment 75 ABCC7 p.Ser549Arg An interesting feature of the clinical presentation associated with S549R in the UAE is that none of the 15 homozygous patients had presented with meconium ileus at birth. Login to comment 88 ABCC7 p.Ser549Arg Detection of the S549R mutation is thus imperative in these cystic fibrosis children, as aggressive treatment and management modalities should be instigated as soon as possible in order to increase the patient's chances of survival. Login to comment