ABCA12 p.Leu2459Arg
| Predicted by SNAP2: | A: N (53%), C: N (61%), D: D (80%), E: D (75%), F: D (59%), G: D (71%), H: D (66%), I: N (72%), K: D (63%), M: N (87%), N: D (66%), P: D (75%), Q: D (63%), R: D (71%), S: D (63%), T: N (53%), V: N (93%), W: N (61%), Y: D (63%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D, |
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[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.
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No. Sentence 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.
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ABCA12 p.Leu2459Arg 17082782:60:72
status: NEW61 7436G>A 2,490 Exon 51Exon 50 Short name p. Arg2479Lys WT ∆4 "06;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 HIKNHK NHK HIK 289 kDa298 kDa 250 kDa p.Arg2479Lys d c b a Figure 2.
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ABCA12 p.Leu2459Arg 17082782:61:72
status: NEW