ABCMdb

ABCC7 p.Asn416Ser

CF databases:	c.1247A>G , p.Asn416Ser (CFTR1) ? , The mutation was detected by DGGE and DHPLC and identified by direct sequencing. We have seen it only once, in over 3000 chromosomes analysed by DGGE.
Predicted by SNAP2:	A: N (61%), C: N (66%), D: N (87%), E: N (61%), F: N (57%), G: N (78%), H: N (93%), I: N (61%), K: N (61%), L: N (57%), M: N (66%), P: N (57%), Q: N (78%), R: N (61%), S: N (87%), T: N (93%), V: N (87%), W: N (57%), Y: N (61%),
Predicted by PROVEAN:	A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N,

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Publications
[hide] A 10-year large-scale cystic fibrosis carrier scre... J Cyst Fibros. 2010 Jan;9(1):29-35. Epub 2009 Nov 7. Picci L, Cameran M, Marangon O, Marzenta D, Ferrari S, Frigo AC, Scarpa M
A 10-year large-scale cystic fibrosis carrier screening in the Italian population.
J Cyst Fibros. 2010 Jan;9(1):29-35. Epub 2009 Nov 7., [PMID:19897426]

Abstract [show]
BACKGROUND: Cystic Fibrosis (CF) is one of the most common autosomal recessive genetic disorders, with the majority of patients born to couples unaware of their carrier status. Carrier screenings might help reducing the incidence of CF. METHODS: We used a semi-automated reverse-dot blot assay identifying the 47 most common CFTR gene mutations followed by DGGE/dHPLC analysis. RESULTS: Results of a 10-year (1996-2006) CF carrier screening on 57,999 individuals with no prior family history of CF are reported. Of these, 25,104 were couples and 7791 singles, with 77.9% from the Italian Veneto region. CFTR mutations were found in 1879 carriers (frequency 1/31), with DeltaF508 being the most common (42.6%). Subjects undergoing medically assisted reproduction (MAR) had significantly (p<0.0001) higher CF carrier frequency (1/22 vs 1/32) compared to non-MAR subjects. CONCLUSIONS: If coupled to counselling programmes, CF carrier screening tests might help reducing the CF incidence.

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Sentences [show]
No. Sentence Comment
131 Aminoacid change Nucleotide change A349V 1178C→T D372E 1251T→G D674V 2153A→T D806G 2549A→G I586V 1888A→G I807V 2551A→G I840T 2651T→C L1335F 4135C→T L1414S 4373T→C L1480P 4571T→C M348T 1175T→C N416S 1379A→G P1290T 4000C→T P355S 1195C→T Q1268R 3935A→G Q1352E 4186C→G S431G 2423A→G S660T 2110T→A S911R 2865T→G T1263A 3919A→G T788I 2495C→T V920L 2890G→T Y1381H 4273T→C Y84H 382T→C two CFTR mutations and who had not been previously diagnosed with CF [29]. Login to comment

[hide] Influence of the duplication of CFTR exon 9 and it... J Mol Diagn. 2009 Sep;11(5):488-93. El-Seedy A, Dudognon T, Bilan F, Pasquet MC, Reboul MP, Iron A, Kitzis A, Ladeveze V
Influence of the duplication of CFTR exon 9 and its flanking sequences on diagnosis of cystic fibrosis mutations.
J Mol Diagn. 2009 Sep;11(5):488-93., [PMID:19710401]

Abstract [show]
The DNA sequences of seven regions in the human genome were examined for sequence identity with exon 9 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is mutated in cystic fibrosis, and its intronic boundaries. These sequences were 95% to 96% homologous. Based on this nucleotide sequence similarity, PCR primers for CFTR exon 9 can potentially anneal with other homologous sequences in the human genome. Sequence alignment analysis of the CFTR exon 9 homologous sequences revealed that five registered mutations in the Cystic Fibrosis Mutation Database may be due to the undesired annealing of primers to a homologous sequence, resulting in inappropriate PCR amplification. For this reason, we propose that certain pseudomutations may result from the similarity between CFTR exon 9 (and its flanking introns) and related sequences in the human genome. Here we show that two mutations previously described in the CFTR database (c.1392 + 6insC; c.1392 + 12G>A) were inappropriately attributed to two individuals who sought carrier testing. A more detailed study by either direct sequencing or subcloning and sequencing of PCR products using specially designed primers revealed that these apparent mutations were not, in fact, present in CFTR. In addition, we present new PCR conditions that permit specific amplification of CFTR exon 9 and its flanking regions.

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Sentences [show]
No. Sentence Comment
99 Several variations have been identified in exon 9, including four possible mutations shown in Figure 2A: p.Lys464Asn, c.1328_1329delAT, c.1235delC, and p.Asn416ser (http://www.genet.sickkids.on.ca/cftr/; last accessed 24/12/2008) [Personal communications: p.Lys464Asn (E. Bleth, V. Gaston, P. Gautry), c.1328_1329delAT (T. Bienvenu, L. Tchertkoff, C. Cazeneuve, C Beldjord), c.1235delC (C. Fe´rec), and p.Asn416Ser (L. Picci, M. Cameran, O. Marangon, D. Marzenta, M. Scarpa)]. Login to comment
134 c.1328_1329delAT 1460delAT Deletion of AT from 1328 Exon 9 (no. 10) Frameshift c.1235delC 1367delC Deletion of C at 1235 Exon 9 (no. 10) Frameshift p.Asn416Ser N416S A to G at 1247 Exon 9 (no. 10) Asn to Ser at 416 c.1392 ϩ 6insC; c.1392 ϩ 12GϾA 1524 ϩ 6insC 1524 ϩ 12GϾA Insertion of C after 1392 ϩ 6, G to A at 1392 ϩ 12 Intron 9 (no. 10) mRNA splicing defect? Login to comment
145 These include p.Lys464Asn, c.1328_1329delAT, c.1235delC, and p.Asn416Ser in exon 9, and c.1392 ϩ 6insC; c.1392 ϩ 12GϾA in intron 9. Login to comment

[hide] Consequences of partial duplications of the human ... J Cyst Fibros. 2013 Jul;12(4):407-10. doi: 10.1016/j.jcf.2012.11.006. Epub 2012 Dec 21. El-Seedy A, Pasquet MC, Bienvenu T, Bieth E, Audrezet MP, Kitzis A, Ladeveze V
Consequences of partial duplications of the human CFTR gene on cf diagnosis: mutations or ectopic variations.
J Cyst Fibros. 2013 Jul;12(4):407-10. doi: 10.1016/j.jcf.2012.11.006. Epub 2012 Dec 21., [PMID:23261175]

Abstract [show]
CFTR exon 10 and its flanking regions are duplicated in the human genome. These duplications present mutations compared to the normal exon 10 sequence. Due to the polymorphic sequence of the 3' intron 9 sequence, it may appear difficult to sequence exon 10 and some mutations described in this exon could, in fact, be variations observed in an ectopic duplicated sequence. In our previous work we described a methodology to carry out PCR only of exon 10 and not of ectopic regions. In this work, we analyzed mutations described in the CF data base as being CFTR mutations but also found in ectopic regions: c.1392G>T, c.1338_1339delAT, c.1235delC, and c.1247A>G. We have shown that these mutations appear to be authentic mutations in CFTR exon 10 and not ectopic variations in analyzed patients. These mutations validate the usefulness of our new strategy in the mutation analysis of this region of CFTR.

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Sentences [show]
No. Sentence Comment
23 Indeed, our previous results suggested that several mutations described in exon 10 and its flanking regions may in fact be ectopic variations from sequences detected in pseudogenes: c.1392GNT (p.Lys464Asn, 1524GNT), c.1338_13 39delAT (p.Ile444X, 1460delAT), c.1235delC (p.Ala412GlufsX 30, 1367delC), and c.1247ANG (p.Asn416Ser, N416S) [4]. Login to comment
83 The c.1247ANG (p.Asn416Ser, N416S) mutation is a transition mutation of c.124 7ANG in exon 10 (Fig. 2b), which causes a change in asparagine to serine at position 416 of the CFTR polypeptide. Login to comment