<i>EDNRB</i>mutations cause Waardenburg syndrome type II in the heterozygous state

Issa, Sarah; Bondurand, Nadège; Faubert, Emmanuelle; Poisson, Sylvain; Lecerf, Laure; Nitschké, Patrick; Deggouj, Naïma; Loundon, Natalie; Jonard, Laurence; David, Albert; Sznajer, Yves; Blanchet, P.; Marlin, Sandrine; Pingault, Véronique

doi:10.1002/humu.23206

Cited by 40 publications

(37 citation statements)

References 40 publications

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“…MIR659, EIF3L, MICALL1, C22orf23, POLR2F, SOX10 and RNU6-900P). 15 Homozygous variants in EDNRB have been reported with WS1. 16 Heterozygous variants in EDNRB have been described in individuals with WS without HD and also with isolated HD.…”

Section: Resultsmentioning

confidence: 99%

Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome

et al. 2018

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Waardenburg syndrome (WS) is a disorder of neural crest cell migration characterized by auditory and pigmentary abnormalities. We investigated a cohort of 14 families (16 subjects) either by targeted sequencing or whole-exome sequencing. Thirteen of these families were clinically diagnosed with WS and one family with isolated non-syndromic hearing loss (NSHL). Intrafamilial phenotypic variability and non-penetrance were observed in families diagnosed with WS1, WS2 and WS4 with pathogenic variants in PAX3, MITF and EDNRB, respectively. We observed gonosomal mosaicism for a variant in PAX3 in an asymptomatic father of two affected siblings. For the first time, we report a biallelic pathogenic variant in MITF in a subject with WS2 and a biallelic variant in EDNRB was noted in a subject with WS2. An individual with isolated NSHL carried a pathogenic variant in MITF. Blended phenotype of NSHL and albinism was observed in a subject clinically diagnosed to have WS2. A phenocopy of WS1 was observed in a subject with a reported pathogenic variant in GJB2, known to cause isolated NSHL. These novel and infrequently reported observations exemplify the allelic and genetic heterogeneity and show phenotypic diversity of WS.

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Section: Resultsmentioning

confidence: 99%

Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome

et al. 2018

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“…The Endothelin receptor A is present in vascular smooth muscle cells and mediates vasoconstriction and proliferation (Gordon et al, ). On the other hand, the Endothelin receptor B is found in the brain, endothelium, and smooth muscle cells and mediates endothelium‐dependent vasodilation through the release of nitric oxide, prostacyclin, and adrenomedullin (a circulating vasodilatory and natriuretic peptide of vascular endothelial and smooth muscle cell origin) (Issa et al, ; Kawasaki‐Nishihara, Nishihara, Nakamura, & Yamamoto, ). Regarding the role of the Endothelin Receptors in development, it has been shown that the Edn1/Ednra cell signaling plays a critical role in the specification, migration and patterning of mandibular identity in post‐migratory NCCs in different animal models such as Xenopus , zebrafish, chick, rat, rabbit and mouse (Bonano et al, ; Clouthier et al, ; Gordon et al, ; Kempf, Linares, Corvol, & Gasc, ; Miller, Schilling, Lee, Parker, & Kimmel, ; Sabrautzki et al, ; Spence, Anderson, Cukierski, & Patrick, ; Treinen, Louden, Dennis, & Wier, ).…”

Section: Chemical Agentsmentioning

confidence: 99%

“…Additionally, overstimulation of beta‐catenin signals in NCCs at the time of their migration, using LiCl treatment, induced nuclear translocation of beta‐catenin and Lef‐1 up‐regulation in these cells and provoked a marked inhibition of cell delamination and migration (de Melker, Desban, & Duband, ). Lithium has also been show to play a role in the onset of auditory‐pigmentary syndromes and in NCPs (Waardenburg Syndrome Type 2 and Tietz Syndrome), which are characterized by sensorineural hearing loss and abnormal pigmentation of the hair and skin (Issa et al, ; Jin & Thibaudeau, ; Leger et al, ; Yasumoto et al, ). Also, in an animal study performed with mouse, in utero treatment with LiCl rescued mandibular molar tooth morphogenesis in mouse embryos lacking activin‐βA (Inhba −/− ) (Jia et al, ; Shan et al, ).…”

Section: Chemical Agentsmentioning

confidence: 99%

The role of teratogens in neural crest development

Cerrizuela

Vega-Lopez

Aybar

2020

Birth Defects Research

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The neural crest (NC), discovered by Wilhelm His 150 years ago, gives rise to a multipotent migratory embryonic cell population that generates a remarkably diverse and important array of cell types during the development of the vertebrate embryo. These cells originate in the neural plate border (NPB), which is the ectoderm between the neural plate and the epidermis. They give rise to the neurons and glia of the peripheral nervous system, melanocytes, chondrocytes, smooth muscle cells, odontoblasts and neuroendocrine cells, among others. Neurocristopathies are a class of congenital diseases resulting from the abnormal induction, specification, migration, differentiation or death of NC cells (NCCs) during embryonic development and have an important medical and societal impact. In general, congenital defects affect an appreciable percentage of newborns worldwide. Some of these defects are caused by teratogens, which are agents that negatively impact the formation of tissues and organs during development. In this review, we will discuss the teratogens linked to the development of many birth defects, with a strong focus on those that specifically affect the development of the NC, thereby producing neurocristopathies.Although increasing attention is being paid to the effect of teratogens on embryonic development in general, there is a strong need to critically evaluate the specific role of these agents in NC development. Therefore, increased understanding of the role of these factors in NC development will contribute to the planning of strategies aimed at the prevention and treatment of human neurocristopathies, whose etiology was previously not considered.

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“…Mutations in several genes implicated in neural crest cell function are responsible for various human developmental defects, such as Waardenburg syndrome, characterized by sensorineural hearing loss and pigmentation anomalies in hair, skin and irises ( Baxter et al, 2004 ; Etchevers et al, 2006 ). Waardenburg syndrome accounts for about 3% of congenital deafness worldwide ( Issa et al, 2017 ). Significantly, many of the genetic mutations associated with human neurocristopathies also occur in rodents, manifesting themselves in the form of reduced and/or altered pigmentation phenotypes.…”

Section: Introductionmentioning

confidence: 99%

A reporter mouse model forin vivotracing andin vitromolecular studies of melanocytic lineage cells and their diseases

2017

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Alterations in melanocytic lineage cells give rise to a plethora of distinct human diseases, including neurocristopathies, cutaneous pigmentation disorders, loss of vision and hearing, and melanoma. Understanding the ontogeny and biology of melanocytic cells, as well as how they interact with their surrounding environment, are key steps in the development of therapies for diseases that involve this cell lineage. Efforts to culture and characterize primary melanocytes from normal or genetically engineered mouse models have at times yielded contrasting observations. This is due, in part, to differences in the conditions used to isolate, purify and culture these cells in individual studies. By breeding ROSAmT/mG and Tyr::CreERT2 mice, we generated animals in which melanocytic lineage cells are identified through expression of green fluorescent protein. We also used defined conditions to systematically investigate the proliferation and migration responses of primary melanocytes on various extracellular matrix (ECM) substrates. Under our culture conditions, mouse melanocytes exhibit doubling times in the range of 10 days, and retain exponential proliferative capacity for 50-60 days. In culture, these melanocytes showed distinct responses to different ECM substrates. Specifically, laminin-332 promoted cell spreading, formation of dendrites, random motility and directional migration. In contrast, low or intermediate concentrations of collagen I promoted adhesion and acquisition of a bipolar morphology, and interfered with melanocyte forward movements. Our systematic evaluation of primary melanocyte responses emphasizes the importance of clearly defining culture conditions for these cells. This, in turn, is essential for the interpretation of melanocyte responses to extracellular cues and to understand the molecular basis of disorders involving the melanocytic cell lineage.

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EDNRBmutations cause Waardenburg syndrome type II in the heterozygous state

Cited by 40 publications

References 40 publications

Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome

Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome

The role of teratogens in neural crest development

A reporter mouse model forin vivotracing andin vitromolecular studies of melanocytic lineage cells and their diseases

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