Genetic Hypomelanoses: Disorders Characterized By Congenital White Spotting ‐ Piebaldism, Waardenburg Syndrome, and Related Genetic Disorders of Melanocyte Development ‐ Clinical Aspects

Spritz, Richard A.

doi:10.1002/9780470987100.ch29

Cited by 3 publications

(3 citation statements)

References 66 publications

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“…Furthermore, such skin growth needs to be considered in reference to the proliferation (cell division) rate of the pigment cells themselves. These mechanisms are likely to be critical in other contexts, including the development of varied pigment patterns within human pathophysiological skin conditions, such as piebaldism 34,35 , where they will act alongside the well-known impact of clonal expansion of pigment cells.…”

Section: Discussionmentioning

confidence: 99%

Differential growth is a critical determinant of zebrafish pigment pattern formation

Kelsh

Yates

2021

Preprint

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The skin patterns of vertebrates are formed by complex interactions between pigment-producing cells during development. Adult zebrafish (Danio rerio), a model organism for investigating the underlying patterning processes, display alternating horizontal blue and golden stripes, generated by the self-organisation of three pigment cell-types. Mathematical studies in which these cells are modelled as individual agents communicating via short- and long-range interactions have produced breakthroughs in the understanding of pattern development. These models, incorporating all experimentally evidenced cell-cell interactions, replicate many aspects of wild-type and mutant zebrafish patterns. Although received wisdom suggested that initial iridophore distribution was pivotal in orienting patterning, here we show that growth can override its influence. Altered growth sequences can generate further pattern modulation, including vertical stripes and maze-like patterns. We demonstrate that ventrally-biased (asymmetric) growth of the skin field explains two key zebrafish pattern development features which are otherwise obscure (dorso-ventral pattern asymmetry, and predominant ventral-to-dorsal migration of melanophores) in wild-type and multiple zebrafish mutants, and in the related species Danio nigrofasciatus. By identifying biased growth as a novel patterning mechanism, our study will inform future investigations into the mechanisms and evolution of fish pigment patterning and vertebrate pigment pattern formation. Furthermore, our work has implications for the mechanistic basis of human pigmentation defects.

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Section: Discussionmentioning

confidence: 99%

Differential growth is a critical determinant of zebrafish pigment pattern formation

Kelsh

Yates

2021

Preprint

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“…Since almost all mutations leading to genetic hypopigmentary disorders occur in the EDN1/EDNBR and SCF/c-KIT axis [44] and since there is a synergistic stimulatory effect of EDN1/SCF on cell proliferation and melanization in cultured human melanocytes, it is conceivable that blocking either EDN1/EDNBR or SCF/c-KIT signaling could prevent hyperpigmentation due to the coordinately increased expression of EDN1 and SCF because a synergistic stimulatory effect fails to occur. Therefore, we attempted to achieve anti-pigmenting effects on SLs by blocking the EDN/EDNBR signaling lineage.…”

Section: Therapeutic Topical Treatment Approachesmentioning

confidence: 99%

Melanocyte Activation Mechanisms and Rational Therapeutic Treatments of Solar Lentigos

Imokawa

2019

IJMS

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To characterize the pathobiology of solar lentigos (SLs), analyses by semiquantitative RT-PCR, Western blotting, and immunohistochemistry revealed the upregulated expression of endothelin (EDN)-1/endothelin B receptors (EDNBRs), stem cell factor (SCF)/c-KIT, and tumor necrosis factor (TNF)α in the lesional epidermis, which contrasted with the downregulated expression of interleukin (IL) 1α. These findings strongly support the hypothesis that previous repeated UVB exposure triggers keratinocytes to continuously produce TNFα. TNFα then stimulates the secretion of EDNs and the production of SCF in an autocrine fashion, leading to the continuous melanogenic activation of neighboring melanocytes, which causes SLs. A clinical study of 36 patients with SLs for six months treated with an M. Chamomilla extract with a potent ability to abrogate the EDN1-induced increase in DNA synthesis and melanization of human melanocytes in culture revealed a significant improvement in pigment scores and color differences expressed as L values. Another clinical study using a tyrosinase inhibitor L-ascorbate-2-phosphate 3 Na (ASP) demonstrated that L values of test lotion (6% APS)-treated skin significantly increased in SLs and in non-lesional skin with a significantly higher ΔL value in SLs when compared with non-lesional skin. The sum of these findings strongly suggests that combined topical treatment with EDN signaling blockers and tyrosinase inhibitors is a desirable therapeutic choice for SLs.

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“…hypopigmentation of the hair, skin and eyes; congenital sensorineural hearing loss; presence of dystopia canthorum, lateral displacement of the ocular inner canthi; and upper limb abnormalities) and Hirschsprung disease. WS4 is caused by a heterozygous mutation in the transcription factor SOX10 or by a homozygous mutation in EDN3 or its receptor, EDNRB . SOX10 mutations are specifically associated with a more severe phenotype known as PCWH, characterized by peripheral demyelinating neuropathy, central dysmyelination, WS and Hirschsprung disease.…”

Section: Introductionmentioning

confidence: 99%

Pediatric case report: Clinical profile of a patient with PCWH with p.Q377X nonsense mutation in the SOX10 gene

Oshimo

Fukai

Abe

et al. 2012

The Journal of Dermatology

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We report the case of a Japanese patient with PCWH, a neurological variant of Waardenburg type 4. Direct sequencing of the genomic DNA obtained from peripheral leukocytes revealed the p.Q377X nonsense mutation in the SOX10 gene. The patient had mottled hypopigmented macules on the trunk since birth; such macules have not been described previously. The so-called "white forelock", a triangular or diamond shaped leukoderma on the forehead, was absent. We also reviewed and summarized the outcomes of 23 patients with Waardenburg syndrome type 4, PCWH and Yemenite deaf-blind hypopigmentation syndrome, in which SOX10 mutations were identified. Among them, 17 cases were reported to have hypopigmented skin macule(s). The five patients who had the white forelock had PCWH with severe neurological complications. Paradoxically, two cases had hyperpigmented spots. Heterochromia of the iris was reported in four patients.

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Genetic Hypomelanoses: Disorders Characterized By Congenital White Spotting ‐ Piebaldism, Waardenburg Syndrome, and Related Genetic Disorders of Melanocyte Development ‐ Clinical Aspects

Cited by 3 publications

References 66 publications

Differential growth is a critical determinant of zebrafish pigment pattern formation

Differential growth is a critical determinant of zebrafish pigment pattern formation

Melanocyte Activation Mechanisms and Rational Therapeutic Treatments of Solar Lentigos

Pediatric case report: Clinical profile of a patient with PCWH with p.Q377X nonsense mutation in the SOX10 gene

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