Biology of human melanocyte development, Piebaldism, and Waardenburg syndrome

Saleem, Mohamed

doi:10.1111/pde.13713

Cited by 40 publications

(53 citation statements)

References 176 publications

(275 reference statements)

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“…WS is a rare disease of great importance, particularly in the pediatric population [6]. This unique inherited disorder is characterized by pigmentary abnormalities, deafness, and neural crest-derived tissue defect [7]. Several different gene mutations (insertion, deletion, frameshifts, missense, and nonsense mutations) can cause WS [8].…”

Section: Discussionmentioning

confidence: 99%

Waardenburg Syndrome Type-II in Twin Siblings: An Unusual Audio-Pigmentary Disorder

Masood

Jalil

jan

et al. 2020

Cureus

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Waardenburg syndrome (WS) is an interesting inherited audio-pigmentary disorder. The syndrome shows no gender, racial, or ethnic predilection. This unique disorder is characterized by pigmentary abnormalities, deafness, and neural crest-derived tissue defect. WS can be recognized by some specific clinical features that appear after birth; not all affected individuals possess all the clinical features. It has four clinical sub types based on the mutant gene and characteristic morphology. These morphological features are broad nasal root, white forelock, the difference in the colour of eyes, congenital leukoderma, and sensorineural deafness. We report an interesting case of WS in twin boys who fulfill the criteria of WS-II. Our cases have four major criteria (white forelock, heterochromia, sensorineural hearing loss, first degree relative with WS), and 1 minor criterion to establish the diagnosis of WS-II. Most clinical features of WS-II except sensorineural deafness are benign and do not need any intervention but severe deafness can be a serious problem. The current report is unique and is a rare case of WS in twin infants. We present this case for its rarity, relative paucity of literature, and also to emphasize the clinical presentation of this extremely rare disease in twins.

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Section: Discussionmentioning

confidence: 99%

Waardenburg Syndrome Type-II in Twin Siblings: An Unusual Audio-Pigmentary Disorder

Masood

Jalil

jan

et al. 2020

Cureus

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“…These target genes are directly or indirectly involved in melanin synthesis, among which MITF is a key regulatory gene for melanocyte development and melanin synthesis. SOX10 can act alone or directly with PAX3 to generate a coeffect to stimulate and upregulate the expression of MITF [ 12 , 33 ]. The SOX10 c.246delC mutation resulted in early termination of the coding protein sequence at amino acid position 108, and consequently, the mutant protein did not contain the HMG domain and the TA domain.…”

Section: Discussionmentioning

confidence: 99%

“…The main function of melanocytes is to produce melanin to ensure the pigmentation of hair and skin. Melanocytes developed from NCC are widely expressed in the dermis, epidermis, vascular striae of the inner ear, and choroid of the eye, and their developmental disorder will lead to WS characterized by hearing loss and abnormal distribution of pigment in the skin and hair [ 12 , 35 ]. The mutation SOX10 c.246delC (exon 2 in NM_006941) has not been reported according to the Human Gene Mutation Database (HGMD) ( http://www.hgmd.cf.ac.uk/ac/index.php ) [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…With differentiation of the NCC, SOX10 begins to be widely expressed throughout the adult body, such as in the hair follicles, inner ear, iris, and gastrointestinal tract. SOX10 acts as a transcription factor of the microphthalmia-associated transcription factor ( MITF ) gene, and MITF plays a key role in the development of melanocytes [ 12 ]. Currently, it is believed that the aetiology of WS is caused by the abnormal development of NCC [ 7 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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A Novel Spontaneous Mutation of the SOX10 Gene Associated with Waardenburg Syndrome Type II

et al. 2020

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Waardenburg syndrome (WS), also known as auditory-pigmentary syndrome, is the most common cause of syndromic hearing loss. It is responsible for 2–5% of congenital deafness. WS is classified into four types depending on the clinical phenotypes. Currently, pathogenic mutation of PAX3, MITF, EDNRB, EDN3, SNAI2, or SOX10 can cause corresponding types of WS. Among them, SOX10 mutation is responsible for approximately 15% of type II WS or 50% of type IV WS. We report the case of a proband in a Chinese family who was diagnosed with WS type II. Whole exome sequencing (WES) of the proband detected a novel heterozygous spontaneous mutation: SOX10 c.246delC. According to analysis based on nucleic acid and amino acid sequences, this mutation may produce a truncated protein, with loss of the HMG structure domain. Therefore, this truncated protein may fail to activate the expression of the MITF gene, which regulates melanocytic development and plays a key role in WS. Our finding expands the database of SOX10 mutations associated with WS and provides more information regarding the molecular mechanism of WS.

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“…Gene expression of TYR, DCT or TRP-1 is regulated by MITF-M, a master transcription factor in the pigment production, differentiation and survival of melanocytes 6, 7, 8. Congenital defects in MITF-M activity gives rise to a disease called Waardenburg syndrome II in humans or a profound loss of pigmented cells in mice 9, 10.…”

Section: Introductionmentioning

confidence: 99%

Stem Cell Factor-Inducible MITF-M Expression in Therapeutics for Acquired Skin Hyperpigmentation

Yun¹,

Roh²,

Kim³

et al. 2020

Theranostics

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Rationale: Microphthalmia-associated transcription factor M (MITF-M) plays important roles in the pigment production, differentiation and survival of melanocytes. Stem cell factor (SCF) and its receptor KIT stimulate MITF-M activity via phosphorylation at the post-translation level. However, the phosphorylation shortens half-life of MITF-M protein over the course of minutes. Here, we investigated novel hypotheses of (i) whether SCF/KIT can regulate MITF-M activity through gene expression as the alternative process, and (ii) whether chemical inhibition of KIT activity can mitigate the acquired pigmentation in skin by targeting the expression of MITF-M.Methods: We employed melanocyte cultures in vitro and pigmented skin samples in vivo, and applied immunoblotting, RT-PCR, siRNA-based gene knockdown and confocal microscopy.Results: The protein and mRNA levels of MITF-M in epidermal melanocytes and the promoter activity of MITF-M in B16-F0 melanoma cells demonstrated that SCF/KIT could trigger the expression of MITF-M de novo, following the phosphorylation-dependent proteolysis of pre-existing MITF-M protein. SCF/KIT regulated the transcription abilities of cAMP-responsive element-binding protein (CREB), CREB-regulated co-activator 1 (CRTC1) and SRY-related HMG-box 10 (SOX10) but not β-catenin at the MITF-M promoter. Meanwhile, chemical inhibition of KIT activity abolished SCF-induced melanin production in epidermal melanocyte cultures, as well as protected the skin from UV-B-induced hyperpigmentation in HRM2 mice or brownish guinea pigs, in which it down-regulated the expression of MITF-M de novo at the promoter level.Conclusion: We propose the targeting of SCF/KIT-inducible MITF-M expression as a strategy in the therapeutics for acquired pigmentary disorders.

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Biology of human melanocyte development, Piebaldism, and Waardenburg syndrome

Cited by 40 publications

References 176 publications

Waardenburg Syndrome Type-II in Twin Siblings: An Unusual Audio-Pigmentary Disorder

Waardenburg Syndrome Type-II in Twin Siblings: An Unusual Audio-Pigmentary Disorder

A Novel Spontaneous Mutation of the SOX10 Gene Associated with Waardenburg Syndrome Type II

Stem Cell Factor-Inducible MITF-M Expression in Therapeutics for Acquired Skin Hyperpigmentation

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