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Mutations in ABCB6 Cause Dyschromatosis Universalis Hereditaria

Published on Sep 1, 2013in Journal of Investigative Dermatology 6.29
· DOI :10.1038/jid.2013.145
Caie Zhang3
Estimated H-index: 3
(HUST: Huazhong University of Science and Technology),
Duanzhuo Li4
Estimated H-index: 4
(HUST: Huazhong University of Science and Technology)
+ 19 AuthorsYunhua Deng2
Estimated H-index: 2
(HUST: Huazhong University of Science and Technology)
Cite
Abstract
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.
  • References (25)
  • Citations (40)
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References25
Newest
Published on May 24, 2012in PLOS ONE 2.78
Katalin É. Kiss19
Estimated H-index: 19
(MTA: Hungarian Academy of Sciences),
Anna Brózik12
Estimated H-index: 12
(MTA: Hungarian Academy of Sciences)
+ 7 AuthorsGergely Szakács33
Estimated H-index: 33
(MTA: Hungarian Academy of Sciences)
ABCB6, a member of the adenosine triphosphate–binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticulocytes during the final steps of erythroid maturation. Consistent with its presence in exosomes, endogenous ABCB6 is localized to the endo/lysosomal compartment, and is absent from the mitochondria of cell...
Published on Apr 13, 2012in Journal of Biological Chemistry
Dagny Ulrich1
Estimated H-index: 1
,
John R. Lynch31
Estimated H-index: 31
+ 9 AuthorsPhilip M. Potter41
Estimated H-index: 41
Abcb6 is a mammalian mitochondrial ATP-binding cassette (ABC) transporter that regulates de novo porphyrin synthesis. In previous studies, haploinsufficient (Abcb6+/−) embryonic stem cells showed impaired porphyrin synthesis. Unexpectedly, Abcb6−/− mice derived from these stem cells appeared phenotypically normal. We hypothesized that other ATP-dependent and/or -independent mechanisms conserve porphyrins. Here, we demonstrate that Abcb6−/− mice lack mitochondrial ATP-driven import of coproporphy...
Published on Mar 1, 2012in Nature Genetics 25.45
Cheng Wang3
Estimated H-index: 3
(HUST: Huazhong University of Science and Technology),
Yulei Li3
Estimated H-index: 3
(HUST: Huazhong University of Science and Technology)
+ 25 AuthorsMiguel Baquero1
Estimated H-index: 1
(University of Valencia)
Xue Zhang, Jing Yu Liu and colleagues report SLC20A2 mutations in familial idiopathic basal ganglia calcification (IBGC, also known as Fahr disease). These mutations impair the function of the type III phosphate transporter encoded by SLA20A2 and may disturb phosphate homeostasis in the body.
Published on Feb 1, 2012in Nature Genetics 25.45
Virginie Helias7
Estimated H-index: 7
,
Carole Saison7
Estimated H-index: 7
+ 13 AuthorsMaude Le Gall12
Estimated H-index: 12
(UPMC: Pierre-and-Marie-Curie University)
Lionel Arnaud and colleagues identify ABCB6 as the genetic basis of the novel Lan blood group system.
Published on Jan 1, 2012in American Journal of Human Genetics 9.92
Lejin Wang1
Estimated H-index: 1
(PKU: Peking University),
Fei He5
Estimated H-index: 5
(Academy of Medical Sciences, United Kingdom)
+ 22 AuthorsYi Shi14
Estimated H-index: 14
(Academy of Medical Sciences, United Kingdom)
Ocular coloboma is a developmental defect of the eye and is due to abnormal or incomplete closure of the optic fissure. This disorder displays genetic and clinical heterogeneity. Using a positional cloning approach, we identified a mutation in the ATP-binding cassette (ABC) transporter ABCB6 in a Chinese family affected by autosomal-dominant coloboma. The Leu811Val mutation was identified in seven affected members of the family and was absent in six unaffected members from three generations. A L...
Published on Jun 15, 2010in American Journal of Medical Genetics
Xiaohua Dai5
Estimated H-index: 5
(HUST: Huazhong University of Science and Technology),
Yong Gao4
Estimated H-index: 4
(HUST: Huazhong University of Science and Technology)
+ 7 AuthorsLiu J18
Estimated H-index: 18
(HUST: Huazhong University of Science and Technology)
Idiopathic basal ganglia calcification (IBGC) is a neurodegenerative disorder that is characterized by basal ganglia and extrabasal ganglia calcification, and usually inherited in an autosomal dominant pattern. To date, two genetic loci for IBGC were identified on chromosomes 14q and 2q, but further genetic heterogeneity clearly exists. In this study, a large Chinese family with autosomal dominant IBGC was characterized. Linkage analysis excluded the 14q13 and 2q37 loci. The large family was the...
Published on Jan 1, 2010in Nature Cell Biology 17.73
Matias Ostrowski14
Estimated H-index: 14
(Curie Institute),
Nuno Carmo6
Estimated H-index: 6
(IMM: Instituto de Medicina Molecular)
+ 17 AuthorsRui P. Freitas4
Estimated H-index: 4
(IMM: Instituto de Medicina Molecular)
Exosome biogenesis is poorly understood. The small GTPases Rab27a and Rab27b and their effectors, Slp4 and Slac2b, control exosome secretion at different steps by regulating the peripheral localization, retention and docking of exosomal precursors, the multivesicular endosomes.
Published on Aug 1, 2009in Current Opinion in Cell Biology 8.23
Mikael Simons44
Estimated H-index: 44
(GAU: University of Göttingen),
Graça Raposo92
Estimated H-index: 92
Cells release different types of vesicular carriers of membrane and cytosolic components into the extracellular space. These vesicles are generated within the endosomal system or at the plasma membrane. Among the various kinds of secreted membrane vesicles, exosomes are vesicles with a diameter of 40–100 nm that are secreted upon fusion of multivesicular endosomes with the cell surface. Exosomes transfer not only membrane components but also nucleic acid between different cells, emphasizing thei...
Published on May 7, 2008in Clinical Genetics 4.10
M. Stuhrmann2
Estimated H-index: 2
(MHH: Hannover Medical School),
Hans Christian Hennies37
Estimated H-index: 37
(University of Cologne)
+ 9 AuthorsS. Knothe1
Estimated H-index: 1
(MHH: Hannover Medical School)
Dyschromatosis universalis hereditaria (DUH) and dyschromatosis symmetrica hereditaria (DSH) are pigmentary dermatoses most commonly seen in Japan. Both disorders usually show autosomal dominant inheritance, although in some cases autosomal recessive inheritance was reported. DSH was mapped to chromosome 1q21.3, and mutations in the gene ADAR (DSRAD) were identified in Japanese, Chinese and Taiwanese families with autosomal dominant DSH. A second locus for dyschromatosis was mapped on chromosome...
Published on Jan 1, 2008in Journal of Investigative Dermatology 6.29
Hidenori Watabe20
Estimated H-index: 20
(St. Marianna University School of Medicine),
Julio C. Valencia31
Estimated H-index: 31
(NIH: National Institutes of Health)
+ 7 AuthorsVincent J. Hearing68
Estimated H-index: 68
(NIH: National Institutes of Health)
Melanosomes are unique membrane-bound organelles specialized for the synthesis and distribution of melanin. Mechanisms involved in the trafficking of proteins to melanosomes and in the transport of mature pigmented melanosomes to the dendrites of melanocytic cells are being characterized, but details about those processes during early stages of melanosome maturation are not well understood. Early melanosomes must remain in the perinuclear area until critical components are assembled. In this stu...
Cited By40
Newest
Published on May 3, 2019in Cellular and Molecular Life Sciences 7.01
Zsófia Rakvács1
Estimated H-index: 1
(MTA: Hungarian Academy of Sciences),
Nóra Kucsma6
Estimated H-index: 6
(MTA: Hungarian Academy of Sciences)
+ 9 AuthorsJohannes M. Reisecker1
Estimated H-index: 1
(Medical University of Vienna)
ABCB6 belongs to the family of ATP-binding cassette (ABC) transporters, which transport various molecules across extra- and intra-cellular membranes, bearing significant impact on human disease and pharmacology. Although mutations in the ABCB6 gene have been linked to a variety of pathophysiological conditions ranging from transfusion incompatibility to pigmentation defects, its precise cellular localization and function is not understood. In particular, the intracellular localization of ABCB6 h...
Published on Apr 1, 2019in Clinical and Experimental Dermatology 1.77
W. Zhong (PKU: Peking University), Yue Pan5
Estimated H-index: 5
(PKU: Peking University)
+ 3 AuthorsZhimiao Lin13
Estimated H-index: 13
(PKU: Peking University)
Published on Feb 14, 2019in Human Genetics 5.21
Julie Plaisancié6
Estimated H-index: 6
(University of Toulouse),
Fabiola Ceroni2
Estimated H-index: 2
(Oxford Brookes University)
+ 4 AuthorsNicola K. Ragge20
Estimated H-index: 20
(Oxford Brookes University)
Eye formation is the result of coordinated induction and differentiation processes during embryogenesis. Disruption of any one of these events has the potential to cause ocular growth and structural defects, such as anophthalmia and microphthalmia (A/M). A/M can be isolated or occur with systemic anomalies, when they may form part of a recognizable syndrome. Their etiology includes genetic and environmental factors; several hundred genes involved in ocular development have been identified in hum...
Published on Jan 1, 2019in Pharmacological Research 5.57
Jan Skoda5
Estimated H-index: 5
(Masaryk University),
Karolina Borankova1
Estimated H-index: 1
(Masaryk University)
+ 3 AuthorsDes R. Richardson71
Estimated H-index: 71
(Masaryk University)
Abstract Mitochondria play vital roles in various cellular processes, ranging from cellular metabolism to signal transduction and cell death regulation. As these properties are critical for cancer growth, the mitochondrion has recently become an attractive target for anti-cancer therapies. In addition, it has come to light that mitochondria are crucially involved in the regulation of stem cell identity, differentiation and fate. A similar role for mitochondria has been also demonstrated in malig...
Published on Dec 1, 2018
Elizabeth S. Egan15
Estimated H-index: 15
(Stanford University),
Michael P. Weekes24
Estimated H-index: 24
(University of Cambridge)
+ 11 AuthorsSeishi Watanabe1
Estimated H-index: 1
(Gulf Coast Regional Blood Center)
The ATP-binding cassette transporter ABCB6 was recently discovered to encode the Langereis (Lan) blood group antigen. Lan null individuals are asymptomatic, and the function of ABCB6 in mature erythrocytes is not understood. Here, we assessed ABCB6 as a host factor for Plasmodium falciparum malaria parasites during erythrocyte invasion. We show that Lan null erythrocytes are highly resistant to invasion by P. falciparum, in a strain-transcendent manner. Although both Lan null and Jr(a-) erythroc...
Published on Oct 1, 2018in Journal of Molecular Biology 5.07
Ptissam Bergam4
Estimated H-index: 4
(Curie Institute),
Johannes M. Reisecker1
Estimated H-index: 1
+ 4 AuthorsGuillaume van Niel22
Estimated H-index: 22
Abstract Genetically inheritable pigmentation defects provide a unique opportunity to reveal the function of proteins contributing to melanogenesis. Dyschromatosis universalis hereditaria (DUH) is a rare pigmentary genodermatosis associated with mutations in the ABCB6 gene. Here we use optical and electron microscopy imaging combined with biochemical tools to investigate the localization and function of ABCB6 in pigment cells. We show that ABCB6 localizes to the membrane of early melanosomes and...
Published on Jun 1, 2018in British Journal of Dermatology 6.71
Taro Masaki11
Estimated H-index: 11
(Kobe University),
Eiji Nakano5
Estimated H-index: 5
(Kobe University)
+ 5 AuthorsChikako Nishigori25
Estimated H-index: 25
(Kobe University)
Published on Jan 1, 2018
Melanin ist ein wichtiges endogenes Pigment der Haut. Es wird dort von speziellen Zellen, den Melanozyten, die der Neuralleiste entstammen, und in speziellen Organellen, den Melanosomen, gebildet. Das Melanin wird an benachbarte Keratinozyten abgegeben. Dieser komplexe Prozess der Melanogenese, ist zum grosen Teil genetisch determiniert, allerdings auch von exogenen Reizen beeinflussbar, besonders UV-Strahlung. Storungen der Melaninpigmentierung haben deshalb medizinisch bedeutsame Konsequenzen ...
Published on Jan 1, 2018in Aaps Journal 3.54
Rebba C. Boswell-Casteel1
Estimated H-index: 1
(St. Jude Children's Research Hospital),
Yu Fukuda7
Estimated H-index: 7
(St. Jude Children's Research Hospital),
John D. Schuetz67
Estimated H-index: 67
(St. Jude Children's Research Hospital)
Recent findings have discovered how insufficiency of ATP-binding cassette (ABC) transporter, ABCB6, can negatively impact human health. These advances were made possible by, first, finding that ABCB6 deficiency was the genetic basis for some severe transfusion reactions and by, second, determining that functionally impaired ABCB6 variants enhanced the severity of porphyria, i.e., diseases associated with defects in heme synthesis. ABCB6 is a broad-spectrum porphyrin transporter that is capable o...