ABCMdb

PMID: 20522854

Sermet-Gaudelus I, Girodon E, Roussel D, Deneuville E, Bui S, Huet F, Guillot M, Aboutaam R, Renouil M, Munck A, des Georges M, Iron A, Thauvin-Robinet C, Fajac I, Lenoir G, Roussey M, Edelman A
Measurement of nasal potential difference in young children with an equivocal sweat test following newborn screening for cystic fibrosis.
Thorax. 2010 Jun;65(6):539-44., [PubMed]

Sentences

No. Mutations Sentence Comment

84 ABCC7 p.Gln1291Arg ABCC7 p.Arg933Gly A second mutation was subsequently identified in all three (621+3A/G, R933G and Q1291R) while the other two with diagnostic scores in the normal range had no other mutation and were asymptomatic at follow-up. Login to comment 88 ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Glu1418* The tracings of three infants with CF (F508del/E1418X, 6 months old; F508del/F508del, 8 months old; and N1303K/N1303K, 18 months old, respectively) are compared with that of a healthy control (3 years old, negative neonatal screening, sweat Cle at 25 mmol/l, no mutation found at extensive genetic analysis). Login to comment 91 ABCC7 p.Arg117His ABCC7 p.Arg347His Of the three patients with two CFTR mutations in the HIRT-Nl group, one carried a mutation without any clinical consequence (3849+45G/A), while the other two carried F508del in trans with the R347H broad-spectrum mutation, or the CFTR-RD-associated mutation R117H. Login to comment 92 ABCC7 p.Arg117His Five patients with HIRTwere compound heterozygous for the CF-causing mutations F508del and R117H on an intron 8 T7 background. Login to comment 121 ABCC7 p.Arg117His Five children carrying the F508del/R117H;T7 genotypes were investigated. Login to comment 124 ABCC7 p.Arg117His Although we cannot rule out a mutation in a non-coding region or in the promoter region, despite extensive genotyping, these findings suggest that the rare association of CFTR-related clinical symptoms with the F508del/ R117H;T7 genotype may be assessed by NPD measurements.24 25 CONCLUSION Although the clinical significance of CFTR dysfunction in the newborns with HIRT can only be definitively determined through systematic long-term follow-up, our results suggest Table 2 Clinical characteristics of children with hypertrypsinaemia (HIRT) at birth and at follow-up according to the diagnostic score cut-off HIRT-Nl HIRT-CF NPD diagnosis score >0.27 #0.27 p Value No. Login to comment 130 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg347His ABCC7 p.Arg352Gln ABCC7 p.Leu206Trp ABCC7 p.Gly622Asp ABCC7 p.Arg117Cys ABCC7 p.Arg1070Trp ABCC7 p.Trp846* ABCC7 p.Gln1291Arg ABCC7 p.Arg933Gly Table 3 Genotypes of the children with HIRT according to the diagnostic score cut-off in the 21 patients with reliable NPD tests; results after extensive genetic analysis CFTR genotypes Diagnosis score >0.27 (8 patients) £0.27 (13 patients) A/A 0 F508del/621+3A/G F508del/Q1291R A/AB F508del/R347H F508del/R117H;T7 W846X/R117C n¼2 F508del/R1070W 2183AA/G/L206W F508del/3272-26A/G F508del/R117H;T7; n¼4 A/D 0 F508del/R933G G551D/R352Q B/D G622D/3849+45G/A 0 A/0 F508del/0 n¼2 0 0/0 3 0 0, no identified mutation; A, CF-causing mutation; B, mutation associated with cystic CFTR-related disorders; C, mutation with no clinical consequence ; D, mutation of unknown or uncertain clinical relevance; AB, mutation that is associated with a wide phenotypic spectrum that might belong to either group A or B. CFTR, cystic fibrosis transmembrane conductance regulator; HIRT, hypertrypsinaemia; NPD, nasal potential difference. Login to comment