ABCMdb

PMID: 12014388

Padoan R, Bassotti A, Seia M, Corbetta C
Negative sweat test in hypertrypsinaemic infants with cystic fibrosis carrying rare CFTR mutations.
Eur J Pediatr. 2002 Apr;161(4):212-5., [PubMed]

Sentences

No. Mutations Sentence Comment

8 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117Leu ABCC7 p.Leu997Phe ABCC7 p.Ala309Asp Molecular analysis identified the following genotypes: F508del/A309D, F508del/3849+ 10kbCfiT, F508del/R117H (in two patients), R117H/ L997F, and F508del/R117L. Login to comment 14 ABCC7 p.Arg117His ABCC7 p.Ala455Glu ABCC7 p.Asp1152His Diagnostic delay has been reported for patients bearing specific CFTR gene mutations such as R117H, D1152H, 3849+10kbCfiT, A455E and 2789+5GfiA, which were associated with a non-pathological sweat chloride level [3, 6, 9,13]. Login to comment 34 ABCC7 p.Arg117His Genetic analysis performed with PCR/OLA assay identified two other mutations (R117H in three patients and 3849+10kbCfiT in one). Login to comment 35 ABCC7 p.Arg117Leu ABCC7 p.Leu997Phe ABCC7 p.Ala309Asp A subsequent expanded analysis of the CFTR gene, by means of DGGE analysis and sequencing, was performed on the remaining three chromosomes and identified the following CFTR alterations: R117L, L997F, and A309D. Login to comment 38 ABCC7 p.Arg117His However, on a repeat sweat test, only two patients showed abnormal chloride values (patients 1 and 2), although the sweat chloride concentration found in patient 3 (R117H-7T/F508del) was higher than that found in previously performed sweat tests. Login to comment 40 ABCC7 p.Arg117His Patients 1 and 2 presented lung disease and isolated severe nasal polyps respectively, whereas patients 3 and 5 (R117H-7T/F508del) suffered from recurrent upper respiratory infections, showing only bronchial thickening in the lower lobes on a chest X-ray film. Login to comment 42 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117Leu ABCC7 p.Leu997Phe ABCC7 p.Ala309Asp Table 1 Diagnostic features of patients Patient number Sex First IRT (ng/ml) (cut-off) Second IRT (ng/ml) (cut-off) Sweat test chloride (mmol/l) Age at sweat test Age at re-evaluation Symptoms Repeat sweat test chloride (mmol/l) Genotype 1 M 47 (40) 39 (30) 43 4 months 3 years and 3 months Chronic respiratory 64 DF508/A309D 2 M 174 (55) 112 (40) <60 4 months 6 years and 6 months Severe nasal polyposis 68 DF508/3849+ 10kbCfiT 3 F 56 (55) 64 (40) 34 4 months 5 years and 4 months Recurrent upper airways infections 55 DF508/R117H-7T 4 F 84 (80) 102 (40) 55 4 months 4 years No symptoms Not determined R117H-5T/L997F 5 F 142 (80) 81 (40) 37 3 months 20 months Recurrent upper airways infections 47 DF508/R117H-7T 6 F 90 (80) 55 (40) 36 2 months 18 months No symptoms 49 DF508/R117L Discussion Our retrospective evaluation of patients diagnosed beyond 1 year of age at our centre over a ca. 6-year period shows that hypertrypsinaemic newborns carrying at least one ''mild`` CFTR mutation may have a chloride sweat test below 60 mmol/l and a delayed CF diagnosis. Login to comment 43 ABCC7 p.Arg117His ABCC7 p.Arg117Leu ABCC7 p.Leu997Phe ABCC7 p.Ala309Asp Rare mutations in the CFTR gene were identified in six patients showing increased b-IRT on newborn screening and a normal sweat test: R117H (three cases), R117L, A309D, L997F and the intronic alteration 3849+10kbCfiT. Login to comment 44 ABCC7 p.Arg117His ABCC7 p.Arg117Leu ABCC7 p.Leu997Phe ABCC7 p.Ala309Asp In the whole CF population followed at the Milan CF Centre (580 patients), R117L, A309D and L997F have never been identified before, whereas R117H and 3849+10kbCfiT account for only 0.51% and 0.68% of alleles, respectively. Login to comment 49 ABCC7 p.Arg117His ABCC7 p.Arg117His PolyT testing has been recommended to establish whether the R117H mutation is associated with CF, however in our patients the R117H-7T allele was associated with persistent neonatal hypertrypsinaemia, a sweat chloride in the upper borderline range, and recurrent respiratory symptoms in the first years of life. Login to comment 50 ABCC7 p.Arg117His The diagnosis of CF was made in patient 3 after the birth of a sister with persistent neonatal hypertrypsinaemia, a sweat test above 30 mmol/l chloride and the same genotype (F508del/R117H-7T). Login to comment