ABCC6 p.Ser398Arg
| LOVD-ABCC6: |
p.Ser398Arg
D
p.Ser398Gly D |
| Predicted by SNAP2: | A: D (80%), C: D (80%), D: D (91%), E: D (91%), F: D (91%), G: D (75%), H: D (85%), I: D (91%), K: D (95%), L: D (91%), M: D (91%), N: N (61%), P: D (91%), Q: D (75%), R: D (91%), T: D (85%), V: D (91%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | A: D, C: D, D: N, E: N, F: D, G: N, H: N, I: D, K: N, L: D, M: D, N: N, P: D, Q: N, R: D, T: N, V: D, W: D, Y: D, |
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[hide] Novel clinico-molecular insights in pseudoxanthoma... Hum Mutat. 2008 Jan;29(1):205. Vanakker OM, Leroy BP, Coucke P, Bercovitch LG, Uitto J, Viljoen D, Terry SF, Van Acker P, Matthys D, Loeys B, De Paepe A
Novel clinico-molecular insights in pseudoxanthoma elasticum provide an efficient molecular screening method and a comprehensive diagnostic flowchart.
Hum Mutat. 2008 Jan;29(1):205., [PMID:18157818]
Abstract [show]
Pseudoxanthoma elasticum (PXE) is a heritable connective tissue disorder characterized by ocular, cutaneous and cardiovascular manifestations. It is caused by mutations in the ABCC6 gene (chr. 16p13.1), encoding a transmembrane transporter protein, the substrate and biological function of which are currently unknown. A comprehensive clinical and molecular study of 38 Belgian PXE probands and 21 relatives (4 affected and 17 carriers) was performed. An extensive clinical evaluation protocol was implemented with serial fundus, skin and cardiovascular evaluation. We report on 14 novel mutations in the ABCC6 gene. We observed extensive variability in severity of both cutaneous and ocular lesions. The type of skin lesion however usually remained identical throughout the evolution of the disorder, while ophthalmological progression was mainly due to functional decline. Peripheral artery disease (53%) and stroke (15%) were significantly more prevalent than in the general population (10-30% and 0.3-0.5% respectively). Interestingly, we also observed a relatively high incidence of subclinical peripheral artery disease (41%) in our carrier population. We highlight the significance of peripheral artery disease and stroke in PXE patients as well as the subclinical manifestations in carriers. Through follow-up data we gained insight into the natural history of PXE. We propose a cost- and time-efficient two-step method of ABCC6 analysis which can be used in different populations. Additionally, we created a diagnostic flowchart and attempted to define the role of molecular analysis of ABCC6 in the work-up of a PXE patient.
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No. Sentence Comment
83 Genotype and Phenotype of 42 Belgian PXE Patients Patient S e x Age/Clinical score at initial presentation Age/Clinical score at most recent follow-up Mutations* Allele 1 Allele 2 01-001 F 52 - S0, E2 65 - S0, E3, HT p.R1141X c.3421C>T p.R760Q c.2279G>A 02-001 M 18 - S1, E2, VR-I 18 - S1, E2, VR-I p.R1141X c.3421C>T p.R1141X c.3421C>T 03-001 F 59 - S1, E4 75 - S1, E4, HT, IC, VR-I p.R1141X c.3421C>T p.N793L c.2379C>G 04-001 F 36 - S3, E2 36 - S3, E2 p.N466Y c.1396A>T p.R1339H c.4016G>A 05-001 F 26 - S1, E4 43 - S3, E4, VR-I p.R1141X c.3421C>T p.T364M c.1091C>T 06-001 F 36 - S2, E4 44 - S2, E4, P p.A1303P c.3907G>C None found - 07-001 M 48 - S1, E2, HT 58 - S1, E4, HT p.R1141X c.3421C>T p.R1141X c.3421C>T 08-001 F 26 - S1, E0 44 - S2, E2 p.R1141X c.3421C>T p.R760Q c.2279G>A 09-001 M 49 - S0, E3, P, GIB 65 - S2, E4, P, HT, VR-I, GIB p.A1303P c.3907G>C None found - 10-001 F 46 - S1, E2 63 - S3, E4, HT, AP,VR-I p.R1141X c.3421C>T p.R1141X c.3421C>T 11-001 M 25 - S1, E2, GIB 37 - S1, E3, GIB p.R1141X c.3421C>T None found - 12-001 F 52 - S1, E4, CI, HT, VR-I 52 - S1, E4, IC, HT, VR-I p.R1141X c.3421C>T p.R1141X c.3421C>T 12-002 F 40 - S1, E2, HT, MVP, VR-I 40 - S1, E2, HT, MVP, VR-I p.R1141X c.3421C>T p.R1141X c.3421C>T 13-001 F 65 - S0, E2 80 - S0, E2, P, VR-I p.R1141X c.3421C>T p.R1141X c.3421C>T 13-002 F 57 - S3, E4 73 - S3, E4, HT, CI, VR-I p.R1141X c.3421C>T p.R1141X c.3421C>T 14-001 F 23 - S1, E2 27 - S1, E2 p.S398R c.1194C>G - c.3364delT 15-001 F 27 - S1, E2 27 - S1, E2 p.R1138W c.3412C>T p.R1221H c.3662G>A 16-001 M 51 - S2, E2 54 - S2, E2 p.R1141X c.3421C>T p.R1141X c.3421C>T 17-001 M 42 - S1, E3, IC 58 - S1, E3, IC Del23-29 - p.R518Q c.1553G>A 18-001 M 63 - S1, E4 63 - S1, E4 p.E1400K c.4198G>A None found - 19-001 F 34 - S2, E2 50 - S2, E2 p.A1303P c.3907G>C p.R1398X c.4192C>T 20-001 F 52 - S2, E2, HT, IC, GIB 68 - S2, E4, HT, IC, GIB p.R1141X c.3421C>T None found - 21-001 M 20 - S1, E2 26 - S1, E2 p.R1141X c.3421C>T p.R1141X c.3421C>T 22-001 M 53 - S2, E2, IC, AP 69 - S2, E2, HT, IC, AP p.M751K c.2252T>A p.R1164Q c.3491G>A 23-001 F 20 - S1, E2 27 - S1, E2, P, VR-I p.G666V c.1996G>T - c.1868-5T>G 24-001 M 54 - S1, E2 57 - S1, E2 p.T500P c.1498A>C p.E521D c.1563G>C 25-001 F 50 - S1, E3, HT, MI 57 - S2, E3, HT, MI p.R1141X c.3421C>T p.R1141X c.3421C>T 26-001 M 52 - S2, E4, HT 68 - S2, E4, HT, CI p.M751K c.2252T>A Del23-29 - 27-001 F 61 - S3, E4 68 - S3, E4, P, CI, AP p.R1141X c.3421C>T - c.4104delC Allele 2 28-001 F 31 - S1, E2 32 - S1, E2 - c.1674DelC p.R765W c.2293C>T Patient S e x Age/Clinical score at initial presentation Age/Clinical score at most recent follow-up Mutations* Allele 1 Allele 2 29-001 M 30 - S1, E3 32 - S1, E3 p.E125K c.373G>A p.L1025P c.3074T>C 30-001 M 65 - S0, E2, HT, CI, MI 66 - S0, E2, HT, CI, MI p.G1405S c.4213G>A None found - 31-001 F 38 - S1, E4 39 - S1, E4 p.R1141X c.3421C>T Del23-29 - 32-001 M 22 - S1, E2 36 - S1, E2 p.R1141X c.3421C>T p.R518Q c.1553G>A 33-001 F 45 - S2, E3, P 61 - S2, E3, P, VR-II p.R1141X c.3421C>T p.R1141X c.3421C>T 34-001 F 65 - S1, E4, HT 81 - S1, E4, HT, AP p.R1141X c.3421C>T p.T1301I c.3902C>T 35-001 F 62 - S2, E2 78 - S2, E2, HT - c.175_179del p.G1354R c.4060G>C 35-002 F 58 - S2, E2 74 - S2, E4 - c.175_179del p.G1354R c.4060G>C 35-003 M 67 - S2, E2 79 - S2, E3, HT, VR-I - c.175_179del p.G1354R c.4060G>C 36-001 M 53 - S1, E4 59 - S1, E4, HT, AP p.R1114H c.3341G>A p.Q1237X c.3709C>T 37-001 M 18 - S3, E2 18 - S3, E2 p.Q981H c.2943G>T - c.3507-3C>A 38-001 F 27 - S1, E2 27 - S1, E2 p.G1263R c.3787G>A - c.4182delG Table 1 represents the sex of all patients (M = male; F= female) and the age (in years - italics), respectively at initial presentation and last follow-up.
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ABCC6 p.Ser398Arg 18157818:83:1434
status: NEW[hide] Added value of infrared, red-free and autofluoresc... Br J Ophthalmol. 2010 Apr;94(4):479-86. Epub 2009 Sep 1. De Zaeytijd J, Vanakker OM, Coucke PJ, De Paepe A, De Laey JJ, Leroy BP
Added value of infrared, red-free and autofluorescence fundus imaging in pseudoxanthoma elasticum.
Br J Ophthalmol. 2010 Apr;94(4):479-86. Epub 2009 Sep 1., [PMID:19726431]
Abstract [show]
PURPOSE: Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder caused by mutations in the ABCC6 gene and primarily affects the oculocutaneous and cardiovascular systems. However, the phenotype, including the ophthalmological manifestations, varies in severity. The present study aims to evaluate the added value of novel funduscopic imaging techniques, such as near-infrared reflectance, red-free and autofluorescence imaging in PXE. METHODS: In 22 molecularly proven PXE patients and 25 obligate carriers, PXE retinopathy was evaluated using funduscopy, white light, red-free, infrared and autofluorescence imaging. RESULTS: At least one characteristic of PXE retinopathy was evident on funduscopy of all eyes. Angioid streaks could be subdivided in those with (brick red) or without (feathered) adjacent RPE alterations. Infrared imaging showed the brick-red-coloured streaks as well-demarcated dark fissures, even when these passed unnoticed on funduscopy. Feathered types were detected as triangular areas of hypoautofluorescence. The peau d'orange was much more visible and much more widespread on infrared imaging, with extension from the posterior pole towards the whole midperiphery. Comets and comet tails were best seen with red-free imaging. CONCLUSIONS: Infrared, red-free and autofluorescence imaging are more sensitive than white light funduscopy and imaging in visualising early retinal signs of PXE. In addition, this specialised imaging allows a better appreciation of the extent of lesions. Hence, such imaging increases the chances of making a correct diagnosis early, and aids in the accurate evaluation of evolution of disease in the ophthalmic follow-up of PXE patients.
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No. Sentence Comment
78 In 55% of fundi (24/44), the Table 1 Ophthalmological characteristics of patients Case Age, sex Eye BCVA AS Pd`O C(T) ODD NV PDT Anti-VEGF ABCC6 mutations 1 61, F OD 2/10 + + + À + + À p.R1459C/e OS 9/10 + + + À + + À 2 43, F OD 12/10 + + + À À À À p.R1141X/p.R1141X OS 12/10 + + + À À À À 3 35, M OD 11/10 + + + À À À À p.E125K/p.L1025P OS 1/300 + + + À + + + 4 21, M OD 10/10 + + + À À À À p.R1141X/p.R1141X OS 10/10 + + + + À À À 5 11, M OD 10/10 À + + À À À À c.3506+2T/C/e 3506+2T/COS 10/10 À + + À À À À 6 55, F OD 1/20 + + + À + À À p.R1141X/p.R1141X OS 1.5/10 + + + À + À À 7 40, M OD 4/10 + + + À + + À p.R265G/p.R1141X OS 1/10 + + + À + + À 8 22, F OD 10/10 + + + À À À À p.R1141X/p.R1141X OS 10/10 + + + À À À À 9 29, F OD 10/10 + + + À À À À p.G1263R/c.4182delGG OS 10/10 + + + À À À À 10 20, M OD 10/10 + + + + À À À c.3507-3C/A/p.T944I OS 10/10 + + + + À À À 11 37, F OD 10/10 + + + + À À À p.Q154R/e OS 9/10 + + + + À À À 12 66, F OD 1/20 + À À À + À À p.R1141X/p.R1141X OS 1/10 + À À À + À À 13 68, F OD 10/10 + À À À À À À p.R760Q/p.R1141X OS 10/10 + À À À À À À 14 68, M OD 2/10 + À + À + À À p.A1303P/p.L946I OS CF + À + À + À À 15 58, F OD 7/10 + + + À + À + p.R1141X/c.4103delC OS CF + + + À + + À 16 62,M OD 1/20 + + + À + À + p.R1141X/p.Q1237X OS CF + + + À + À À 17 47, F OD 10/10 + À À À À À À c.3506+2T/C/e OS 10/10 + À À À À À À 18 54, F OD 10/10 + + + À + À + p.R1141X/p.A1303P OS 10/10 + + + À À À À 19 30, F OD 10/10 + + + À À À À p.S398R/c.3364delT OS 10/10 + + + À À À À 20 39, F OD 12/10 + + + À À À À p.R1141X/e OS 10/10 + + + À À À À 21 30, F OD 10/10 + + + À À À À p.G666R/c.1868-5T/G OS 10/10 + + + + À À À 22 34, M OD 12/10 + + + À À À À c.3364delT/p.R518X OS 12/10 + + + À À À À anti-VEGF, anti-vascular endothelial growth factor antibodies; AS, angioid streaks; BCVA, best-corrected visual acuity (Snellen); CF, counting fingers; C(T), Comet (tails); F, female; M, male; MD, macular degeneration; NV, neovascularisation; ODD, optic disc drusen; Pd`O, Peau d`Orange; PDT, photodynamic therapy.
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ABCC6 p.Ser398Arg 19726431:78:2128
status: NEW