ABCMdb

ABCA12 p.Arg2479Lys

Predicted by SNAP2:	A: N (57%), C: N (53%), D: D (75%), E: D (71%), F: D (66%), G: D (66%), H: N (61%), I: D (63%), K: N (57%), L: D (63%), M: N (53%), N: D (53%), P: D (75%), Q: N (57%), S: N (53%), T: N (78%), V: D (63%), W: D (75%), Y: D (66%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: N, L: D, M: D, N: D, P: D, Q: D, S: D, T: D, V: D, W: D, Y: D,

[switch to compact view]
Comments [show]

None has been submitted yet.

Publications
[hide] DNA-based prenatal diagnosis of harlequin ichthyos... J Invest Dermatol. 2007 Mar;127(3):568-73. Epub 2006 Nov 2. Akiyama M, Titeux M, Sakai K, McMillan JR, Tonasso L, Calvas P, Jossic F, Hovnanian A, Shimizu H
DNA-based prenatal diagnosis of harlequin ichthyosis and characterization of ABCA12 mutation consequences.
J Invest Dermatol. 2007 Mar;127(3):568-73. Epub 2006 Nov 2., [PMID:17082782]

Abstract [show]
Until the identification of ABCA12 as the causative gene, prenatal diagnosis (PD) for harlequin ichthyosis (HI) had been performed by electron microscopic observation of fetal skin biopsy samples. We report the first case of HI DNA-based PD. Direct sequence analysis of ABCA12 revealed that the deceased proband was a compound heterozygote for two novel mutations. The maternal nonsense mutation p.Ser1249Term likely leads to nonsense-mediated messenger RNA decay. The paternal mutation c.7436G>A affects the last codon of exon 50 and was expected to be a splice site mutation. For their third pregnancy, the parents requested PD. Direct sequence analysis of fetal genomic DNA from amniotic fluid cells at 17 weeks gestation revealed the fetus was a compound heterozygote for both mutations. The parents requested the pregnancy to be terminated. Analysis of ABCA12 transcripts of cultured keratinocytes from the abortus showed the presence of six abnormally spliced products from the allele carrying the splice site mutation. Four of them lead to premature termination codons whereas the two others produced shortened proteins missing 21 and 31 amino acids from the second ATP-binding cassette. This report provides evidence for residual ABCA12 expression in HI, and demonstrates the efficiency of early DNA-based PD of HI.

Comments [show]

None has been submitted yet.

Sentences [show]
No. Sentence Comment
54 Transcript p.Arg2479Lys corresponds to the full-length ABCA12 transcript carrying a lysine residue in place of the arginine 2479. Login to comment
60 Interestingly, transcript D63 predicts a truncated protein deleted from Leucine 2459 to Arginine 2479 (p.Leu2459_Arg2479del) owing to an in WT cDNA c.7436G>A P.Arg2479Lys C.7433_7436del C.7394_7436del C.7387_7436del p.Leu2141_Arg2479del c.7344_7436del p.Ser2130_Ser2478del C.7374_7436del p.Lys2148_Arg2479>LeufsX11 p.Asn2146_Arg2479>Trpfsx13 C.7406_7436del p.Arg2479>LeufsX11 p.Ile2152_Arg2479>LeufsX11 WT protein Amino-acid position Exon 49 2,130 2,460 2,470 2,480 c. Login to comment
61 7436G>A 2,490 Exon 51Exon 50 Short name p. Arg2479Lys WT ∆4 ∆31 ∆43 ∆50 ∆63 ∆93 ∆63 ∆50 ∆43 "06;4 "06;93 750 500 250 3,600 2,400 1,200 0 300 330 360 390 420 0 HIKNHK NHK HIK 289 kDa298 kDa 250 kDa p.Arg2479Lys d c b a Figure 2. Login to comment
68 Splice variants include the correctly spliced product (p.Arg2479Lys) and six aberrantly spliced forms leading to out-of-frame (transcripts D4, D31, D43, and D50) and in-frame (D63 and D93) deletions. Login to comment
72 The peak at 422 bp corresponds to the full-length transcript, arising either from the wild-type alleles (in NHK) or from the allele carrying the p.Ser1249Term null mutation and from the allele carrying the p.Arg2479Lys mutation (in HIK). Login to comment
84 Interestingly, the height of the peak at 422 bp which arises from both the p.Arg2479Lys transcript and from the transcript synthesized from the other ABCA12 allele carrying the p.Ser1249Term mutation is weak, indicating that the amount of both transcripts is low. Login to comment
113 Although, small amounts of a full-length ABCA12 protein carrying the p.Arg2479Lys mutation may theoretically be synthesized, they were not detected. Login to comment
55 Transcript p.Arg2479Lys corresponds to the full-length ABCA12 transcript carrying a lysine residue in place of the arginine 2479. Login to comment
62 7436G>A 2,490 Exon 51 Exon 50 Short name p. Arg2479Lys WT ࢞4 ࢞31 ࢞43 ࢞50 ࢞63 ࢞93 ࢞63 ࢞50 ࢞43 ࢞4 ࢞93 750 500 250 3,600 2,400 1,200 0 300 330 360 390 420 0 HIK NHK NHK HIK 289 kDa 298 kDa 250 kDa p.Arg2479Lys d c b a Figure 2. Login to comment
69 Splice variants include the correctly spliced product (p.Arg2479Lys) and six aberrantly spliced forms leading to out-of-frame (transcripts D4, D31, D43, and D50) and in-frame (D63 and D93) deletions. Login to comment
73 The peak at 422 bp corresponds to the full-length transcript, arising either from the wild-type alleles (in NHK) or from the allele carrying the p.Ser1249Term null mutation and from the allele carrying the p.Arg2479Lys mutation (in HIK). Login to comment
85 Interestingly, the height of the peak at 422 bp which arises from both the p.Arg2479Lys transcript and from the transcript synthesized from the other ABCA12 allele carrying the p.Ser1249Term mutation is weak, indicating that the amount of both transcripts is low. Login to comment
114 Although, small amounts of a full-length ABCA12 protein carrying the p.Arg2479Lys mutation may theoretically be synthesized, they were not detected. Login to comment