ABCMdb

ABCC6 p.Glu1293Lys

LOVD-ABCC6:	p.Glu1293Lys D
Predicted by SNAP2:	A: D (75%), C: D (75%), D: D (75%), F: D (85%), G: D (85%), H: D (80%), I: D (85%), K: D (85%), L: D (85%), M: D (80%), N: D (75%), P: D (91%), Q: D (63%), R: D (91%), S: D (75%), T: D (80%), V: D (80%), W: D (91%), Y: D (85%),
Predicted by PROVEAN:	A: D, C: D, D: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: N, R: D, S: D, T: D, V: D, W: D, Y: D,

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Publications
[hide] Elastosis perforans serpiginosa-like pseudoxanthom... Br J Dermatol. 2005 Aug;153(2):431-4. Meyer S, Zanardo L, Kaminski WE, Horn P, Schmitz G, Hohenleutner U, Herrmann WA, Landthaler M, Vogt T
Elastosis perforans serpiginosa-like pseudoxanthoma elasticum in a child with severe Moya Moya disease.
Br J Dermatol. 2005 Aug;153(2):431-4., [PMID:16086762]

Abstract [show]
A 2-year-old girl with Moya Moya disease who had relapsing cerebrovascular strokes presented with loose skin folds, 'chicken' skin appearance and perforating elastosis serpiginosa-like lesions in the genitocrural region. Histologically, calcified material perforating the epidermis and adjacent short curled and mineralized elastic fibres suggested a variant of pseudoxanthoma elasticum (PXE). As PXE is known to be caused by various mutations in the transmembrane transporter ABCC6 gene, we hypothesized that a novel ABCC6 mutation may underlie this unique combination of PXE and elastopathic vascular damage. Therefore, the complete ABCC6 coding region of the patient and her parents was screened for genetic alterations. No bona fide disease-causing mutation of ABCC6 could be found in the child and in her parents. However, two novel allelic amino acid substitutions (Arg1273Lys and Glu1293Lys; exon 27) were found in the girl and her father, localized in close proximity to the region that codes for the functionally critical second nucleotide-binding fold of ABCC6. Although a causal involvement of these amino acid substitutions could not be proven based on this study, both heterozygote substitutions may possibly have interacted with other undetected recessive maternal ABCC6 changes in the child. To the best of our knowledge, this is the first report of an association between early-onset PXE and severe Moya Moya syndrome possibly related to ABCC6 changes.

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Sentences [show]
No. Sentence Comment
7 However, two novel allelic amino acid substitutions (Arg1273Lys and Glu1293Lys; exon 27) were found in the girl and her father, localized in close proximity to the region that codes for the functionally critical second nucleotide-binding fold of ABCC6. Login to comment
51 These comprise three adjacent amino acid substitutions in exon 27 (Arg1268Gln, Arg1273Lys and Glu1293Lys) and a single Arg1418Gln exchange in exon 30 (Fig. Login to comment
53 The Arg1268Gln substitution, which results from a G fi A nucleotide exchange in position 3803, was found in both the index patient and her healthy father. This substitution has previously been suggested to be causatively linked to PXE,9 but was later recognized as a common polymorphism with significant allelic frequency.10 In contrast, the Arg1273Lys and Glu1293Lys substitutions in exon 27 are new and have not previously been reported. Login to comment
54 Of particular interest is the Glu1293Lys substitution, which was detected in both the proposita and her father. This substitution not only replaces a negatively charged amino acid with a positively charged one, but is also localized immediately upstream of the functionally critical 'Walker A` motif.11 The fact that the 33-year-old father did not show signs of either PXE or vascular failure (mean age at onset of PXE is approximately 13 years12,13 ) does not necessarily contradict a causative role of the aforementioned substitutions, because PXE is nearly always autosomal recessive. Login to comment
72 Novel amino acid substitutions of the ABCC6 gene (Arg1273Lys and Glu1293Lys) in exon 27 were found in the proposita and her father. Login to comment