ABCB6 p.Leu356Pro
| ClinVar: |
c.1067T>C
,
p.Leu356Pro
D
, Pathogenic
|
| Predicted by SNAP2: | A: D (71%), C: D (53%), D: D (85%), E: D (80%), F: D (66%), G: D (85%), H: D (80%), I: D (59%), K: D (85%), M: N (82%), N: D (85%), P: D (85%), Q: D (71%), R: D (80%), S: D (80%), T: D (75%), V: D (53%), W: D (80%), Y: D (80%), |
| 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: D, W: D, Y: D, |
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[hide] Mutations in ABCB6 cause dyschromatosis universali... J Invest Dermatol. 2013 Sep;133(9):2221-8. doi: 10.1038/jid.2013.145. Epub 2013 Mar 21. Zhang C, Li D, Zhang J, Chen X, Huang M, Archacki S, Tian Y, Ren W, Mei A, Zhang Q, Fang M, Su Z, Yin Y, Liu D, Chen Y, Cui X, Li C, Yang H, Wang Q, Wang J, Liu M, Deng Y
Mutations in ABCB6 cause dyschromatosis universalis hereditaria.
J Invest Dermatol. 2013 Sep;133(9):2221-8. doi: 10.1038/jid.2013.145. Epub 2013 Mar 21., [PMID:23519333]
Abstract [show]
Dyschromatosis universalis hereditaria (DUH) is a pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body. No causative genes have been reported to date. In this study, we investigated a large five-generation Chinese family with DUH. After excluding the two known DUH loci, we performed genome-wide linkage analysis and identified a DUH locus on chromosome 2q33.3-q36.1 with a maximum LOD score of 3.49 with marker D2S2382. Exome sequencing identified a c.1067T>C (p.Leu356Pro) mutation in exon 3 of ABCB6 (ATP-binding cassette subfamily B, member 6) in the DUH family. Two additional missense mutations, c.508A>G (p.Ser170Gly) in exon 1 and c.1736G>A (p.Gly579Glu) in exon 12 of ABCB6, were found in two out of six patients by mutational screening using sporadic DUH patients. Immunohistologic examination in biopsy specimens showed that ABCB6 is expressed in the epidermis and had a diffuse cytoplasmic distribution. Examination of subcellular localization of wild-type ABCB6 in a B16 mouse melanoma cell line revealed that it is localized to the endosome-like compartment and dendrite tips, whereas disease-causing mutations of ABCB6 resulted in its retention in the Golgi apparatus. Our studies identified ABCB6 as the first pathogenic gene associated with DUH. These findings suggest that ABCB6 may be a physiological factor for skin pigmentation.
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No. Sentence Comment
3 After excluding the two known DUH loci, we performed genome-wide linkage analysis and identified a DUH locus on chromosome 2q33.3-q36.1 with a maximum LOD score of 3.49 with marker D2S2382. Exome sequencing identified a c.1067T4C (p.Leu356Pro) mutation in exon 3 of ABCB6 (ATP-binding cassette subfamily B, member 6) in the DUH family.
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ABCB6 p.Leu356Pro 23519333:3:233
status: NEW55 Mutation of the ABCB6 gene in DUH patients The c.1067T4C mutation in ABCB6 leads to a proline to leucine substitution at codon 356 (p.Leu356Pro) in the ABCB6 protein.
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ABCB6 p.Leu356Pro 23519333:55:134
status: NEW82 The wild-type ABCB6 and three mutant forms of ABCB6 (p.Ser170Gly, p.Leu356Pro, and p.Gly579Glu) were tagged with enhanced green fluorescent protein (EGFP) fusion proteins and then transfected into mouse B16 cells, respectively. The localization of the various fusion proteins was determined by confocal microscopy.
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ABCB6 p.Leu356Pro 23519333:82:68
status: NEW116 (a) The mutations in ABCB6 and their Sanger sequencing tracing, including c.1067T4C (p.Leu356Pro) (reverse complement), c.508A4G (p.Ser170Gly), and c.1736G4A (p.Gly579Glu).
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ABCB6 p.Leu356Pro 23519333:116:87
status: NEW138 Genotypes were analyzed by the Gene ABCB6 GaIT DAPI Merge WT Ser170Gly Leu356Pro Gly579Glu Figure 3.
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ABCB6 p.Leu356Pro 23519333:138:71
status: NEW171 Next, we performed site-directed mutagenesis to generate the three ABCB6 mutations associated with DUH (p.Ser170Gly, p.Leu356Pro, and p.Gly579Glu).
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ABCB6 p.Leu356Pro 23519333:171:119
status: NEW[hide] Novel mutations of ABCB6 associated with autosomal... PLoS One. 2013 Nov 5;8(11):e79808. doi: 10.1371/journal.pone.0079808. eCollection 2013. Cui YX, Xia XY, Zhou Y, Gao L, Shang XJ, Ni T, Wang WP, Fan XB, Yin HL, Jiang SJ, Yao B, Hu YA, Wang G, Li XJ
Novel mutations of ABCB6 associated with autosomal dominant dyschromatosis universalis hereditaria.
PLoS One. 2013 Nov 5;8(11):e79808. doi: 10.1371/journal.pone.0079808. eCollection 2013., [PMID:24224009]
Abstract [show]
OBJECTIVE: Dyschromatosis universalis hereditaria (DUH) is a rare heterogeneous pigmentary genodermatosis, which was first described in 1933. The genetic cause has recently been discovered by the discovery of mutations in ABCB6. Here we investigated a Chinese family with typical features of autosomal dominant DUH and 3 unrelated patients with sporadic DUH. METHODS: Skin tissues were obtained from the proband, of this family and the 3 sporadic patients. Histopathological examination and immunohistochemical analysis of ABCB6 were performed. Peripheral blood DNA samples were obtained from 21 affected, 14 unaffected, 11 spouses in the family and the 3 sporadic patients. A genome-wide linkage scan for the family was carried out to localize the causative gene. Exome sequencing was performed from 3 affected and 1 unaffected in the family. Sanger sequencing of ABCB6 was further used to identify the causative gene for all samples obtained from available family members, the 3 sporadic patients and a panel of 455 ethnically-matched normal Chinese individuals. RESULTS: Histopathological analysis showed melanocytes in normal control's skin tissue and the hyperpigmented area contained more melanized, mature melanosomes than those within the hypopigmented areas. Empty immature melanosomes were found in the hypopigmented melanocytes. Parametric multipoint linkage analysis produced a HLOD score of 4.68, with markers on chromosome 2q35-q37.2. A missense mutation (c.1663 C>A, p.Gln555Lys) in ABCB6 was identified in this family by exome and Sanger sequencing. The mutation perfectly cosegregated with the skin phenotype. An additional mutation (g.776 delC, c.459 delC) in ABCB6 was found in an unrelated sporadic patient. No mutation in ABCB6 was discovered in the other two sporadic patients. Neither of the two mutations was present in the 455 controls. Melanocytes showed positive immunoreactivity to ABCB6. CONCLUSION: Our data add new variants to the repertoire of ABCB6 mutations with DUH.
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No. Sentence Comment
135 Mutations of p.S170G, p.L356P, p.G579E in ABCB6 resulted in DUH [12].
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ABCB6 p.Leu356Pro 24224009:135:24
status: NEW[hide] Novel missense mutations of ABCB6 in two chinese f... J Dermatol Sci. 2014 Dec;76(3):255-8. doi: 10.1016/j.jdermsci.2014.08.015. Epub 2014 Sep 11. Lu C, Liu J, Liu F, Liu Y, Ma D, Zhang X
Novel missense mutations of ABCB6 in two chinese families with dyschromatosis universalis hereditaria.
J Dermatol Sci. 2014 Dec;76(3):255-8. doi: 10.1016/j.jdermsci.2014.08.015. Epub 2014 Sep 11., [PMID:25288164]
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51 frameshift mutations in ABCB6 have been reported to be responsible for DUH (p.S170G, p.S322K, p.L356P, p.A453V, p.Q555K, p.G579E and c.459delC) [6-8].
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ABCB6 p.Leu356Pro 25288164:51:96
status: NEW