A rare heterozygous TRAF6 variant is associated with hypohidrotic ectodermal dysplasia

Wisniewski, S.; Trzeciak, Wiesław H.

doi:10.1111/j.1365-2133.2012.10871.x

Cited by 29 publications

(23 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mutations in EDA, EDAR, EDARADD, and TRAF6 all manifest EDA/HED with a clinical phenotype similar to patients with hypomorphic NEMO mutations, although they lack immunodeficiency (Headon et al, 2001; Kere et al, 1996; Wisniewski and Trzeciak, 2012a, b). EDA, which belongs to the tumor necrosis factor family, is expressed on the ectoderm interfollicular cells.…”

Section: Human Geneticsmentioning

confidence: 99%

30 Years of NF-κB: A Blossoming of Relevance to Human Pathobiology

Zhang

Lenardo

Baltimore

2017

Cell

1,617

1,374

View full text Add to dashboard Cite

NF-κB was discovered thirty years ago as a rapidly inducible transcription factor. Since that time it has been found to have a broad role in gene induction in diverse cellular responses, particularly throughout the immune system. Here we summarize elaborate regulatory pathways involving this transcription factor and use recent discoveries in human genetic diseases to place specific proteins within their relevant medical and biological contexts.

show abstract

Section: Human Geneticsmentioning

confidence: 99%

30 Years of NF-κB: A Blossoming of Relevance to Human Pathobiology

Zhang

Lenardo

Baltimore

2017

Cell

1,617

1,374

View full text Add to dashboard Cite

show abstract

“…SASH1 has been reported to be a regulator of TRAF6 ubiquitination, and a de novo heterozygous variant in TRAF6 has recently been identified in patients with hypohydrotic ectodermal dysplasia. [25][26][27] TRAF6, initially identified as a regulator of NF-κB, also has an important role in tumorigenesis, invasion and metastasis, by modulating various signaling pathways. [28][29][30] Finally, because SASH1 has recently been reported as a scaffold molecule implicated in endothelial TLR4 signaling, which is implicated in innate immune responses, we wondered whether palmoplantar keratoderma and alopecia could be due to chronic fungal infection, but this hypothesis was ruled out.…”

Section: Discussionmentioning

confidence: 99%

Autosomal-recessive SASH1 variants associated with a new genodermatosis with pigmentation defects, palmoplantar keratoderma and skin carcinoma

et al. 2014

View full text Add to dashboard Cite

9SASH1 (SAM and SH3 domain-containing protein 1) is a tumor suppressor gene involved in the tumorigenesis of a spectrum of solid cancers. Heterozygous SASH1 variants are known to cause autosomal-dominant dyschromatosis. Homozygosity mapping and whole-exome sequencing were performed in a consanguineous Moroccan family with two affected siblings presenting an unclassified phenotype associating an abnormal pigmentation pattern (hypo-and hyperpigmented macules of the trunk and face and areas of reticular hypo-and hyperpigmentation of the extremities), alopecia, palmoplantar keratoderma, ungueal dystrophy and recurrent spinocellular carcinoma. We identified a homozygous variant in SASH1 (c.1849G4A; p.Glu617Lys) in both affected individuals. Wound-healing assay showed that the patient's fibroblasts were better able than control fibroblasts to migrate. Following the identification of SASH1 heterozygous variants in dyschromatosis, we used reverse phenotyping to show that autosomal-recessive variants of this gene could be responsible for an overlapping but more complex phenotype that affected skin appendages. SASH1 should be added to the list of genes responsible for autosomal-dominant and -recessive genodermatosis, with no phenotype in heterozygous patients in the recessive form, and to the list of genes responsible for a predisposition to skin cancer.

show abstract

“…Recently, a patient who had a classic HED phenotype, including hypodontia and microdontia, was reported to also have a frameshift mutation in the TRAF6 gene (Wisniewski and Trzeciak 2012). The mutant TRAF6 protein was capable of forming a complex with TAK1 and TAB2, similarly to the wildtype protein.…”

Section: Nf-κb Signaling Pathwaymentioning

confidence: 99%

The Gene Network Underlying Hypodontia

2015

View full text Add to dashboard Cite

Mammalian tooth development is a precise and complicated procedure. Several signaling pathways, such as nuclear factor (NF)-κB and WNT, are key regulators of tooth development. Any disturbance of these signaling pathways can potentially affect or block normal tooth development, and presently, there are more than 150 syndromes and 80 genes known to be related to tooth agenesis. Clarifying the interaction and crosstalk among these genes will provide important information regarding the mechanisms underlying missing teeth. In the current review, we summarize recently published findings on genes related to isolated and syndromic tooth agenesis; most of these genes function as positive regulators of cell proliferation or negative regulators of cell differentiation and apoptosis. Furthermore, we explore the corresponding networks involving these genes in addition to their implications for the clinical management of tooth agenesis. We conclude that this requires further study to improve patients' quality of life in the future.

show abstract

A rare heterozygous TRAF6 variant is associated with hypohidrotic ectodermal dysplasia

Abstract: This is the first report of a heterozygous TRAF6 sequence variant associated with symptoms typical of HED.

Cited by 29 publications

References 14 publications

30 Years of NF-κB: A Blossoming of Relevance to Human Pathobiology

30 Years of NF-κB: A Blossoming of Relevance to Human Pathobiology

Autosomal-recessive SASH1 variants associated with a new genodermatosis with pigmentation defects, palmoplantar keratoderma and skin carcinoma

The Gene Network Underlying Hypodontia

Contact Info

Product

Resources

About