ABCC7 p.Ala309Asp
| ClinVar: |
c.926C>G
,
p.Ala309Gly
?
, not provided
|
| CF databases: |
c.925G>A
,
p.Ala309Thr
(CFTR1)
?
,
c.926C>A , p.Ala309Asp (CFTR1) ? , The mutation is the C1058A substitution in exon 7, changing alanine 309 to aspartic acid. This mutation has been detected in the maternal CF chromosome of a PS patient originating from Southern Italy (Sicily) and carrying the [delta]F508 mutation on the other chromosome. c.926C>G , p.Ala309Gly (CFTR1) ? , The above mutation was detected by DGGE using chemical clamps and identified by direct sequencing. It is not found in 100 other non-[delta]F508 CF chromosomes and 100 non-CF chromosomes tested. The patient is from Reunion Island. c.926C>T , p.Ala309Val (CFTR1) ? , |
| Predicted by SNAP2: | C: D (59%), D: D (75%), E: D (75%), F: D (75%), G: D (53%), H: D (85%), I: D (80%), K: D (80%), L: D (71%), M: D (80%), N: D (63%), P: D (75%), Q: D (66%), R: D (75%), S: N (82%), T: N (66%), V: D (63%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] Negative sweat test in hypertrypsinaemic infants w... Eur J Pediatr. 2002 Apr;161(4):212-5. 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., [PMID:12014388]
Abstract [show]
Persistent hypertrypsinaemia in newborn screening for cystic fibrosis (CF) recognises subjects at high risk to be affected. Diagnosis is confirmed by a positive sweat test and/or by the presence of two mutations in the cystic fibrosis transmembrane regulator gene. The aim of the present study was to evaluate the occurrence of a negative sweat test (chloride < 60 mmol/l) during the first months of life, in hypertrypsinaemic infants, which would lead to a delayed diagnosis. We reviewed clinical charts of CF patients born between January 1993 and September 1998, when the neonatal screening programme consisted of an immunoreactive trypsinogen (IRT)/DNA (F508del) + IRT strategy. Laboratory and clinical data were collected for patients diagnosed after 12 months of life. Out of 446,492 newborns, 104 CF patients were diagnosed giving an overall incidence of 1:4293. Of these, six had a blood IRT level above the cut off value (99th percentile) and a negative sweat test in the first trimester of life. At a mean age of 3.5years, the patients were again referred to our CF Centre for re-evaluation in order to confirm or exclude the disorder. Molecular analysis identified the following genotypes: F508del/A309D, F508del/3849 + 10kbC-->T, F508del/R117H (in two patients), R117H/ L997F, and F508del/R117L. CONCLUSION: Infants with cystic fibrosis bearing a spectrum of mild cystic fibrosis transmembrane regulator gene mutations may present as hypertrypsinaemic newborns with a sweat chloride within the normal range. Reference values for normal sweat test during the first months of life should be revised. A wide molecular genetic analysis is recommended for newborns presenting persistent hypertrypsinaemia and a sweat test result > 30 mmol/l in order to diagnose atypical forms of the disease.
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No. Sentence Comment
8 Molecular analysis identified the following genotypes: F508del/A309D, F508del/3849+ 10kbCfiT, F508del/R117H (in two patients), R117H/ L997F, and F508del/R117L.
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ABCC7 p.Ala309Asp 12014388:8:63
status: NEW35 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.
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ABCC7 p.Ala309Asp 12014388:35:205
status: NEW42 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.
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ABCC7 p.Ala309Asp 12014388:42:320
status: NEW43 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.
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ABCC7 p.Ala309Asp 12014388:43:162
status: NEW44 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.
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ABCC7 p.Ala309Asp 12014388:44:82
status: NEW