A new mutation resulting in the truncation of the TRAF6-interacting domain of XEDAR: a possible novel cause of hypohidrotic ectodermal dysplasia: Figure 1

Wisniewski, S.; Trzeciak, Wiesław H.

doi:10.1136/jmedgenet-2012-100877

Cited by 23 publications

(20 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

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

“…14,20 Single mutations in EDA2R and TRAF6 have also been reported to cause HED. 23,24 Previous investigations of potential genotype-phenotype correlations revealed intra-and interfamilial variabilities, not solely explicable by the patients' mutations. 25 The single-nucleotide polymorphism (SNP) rs3827760 (c.1109T4C; p.Val370Ala) in EDA1R, a gain-of-function allele with a high frequency in the East Asian and Native American population, has been associated with increased hair thickness and shovel-shaped incisors 26,27 and was found to attenuate the severity of X-linked HED-related symptoms in a family of Asian origin.…”

Section: Introductionmentioning

confidence: 99%

Mutational spectrum in 101 patients with hypohidrotic ectodermal dysplasia and breakpoint mapping in independent cases of rare genomic rearrangements

2016

View full text Add to dashboard Cite

Hypohidrotic ectodermal dysplasia (HED), a rare and heterogeneous hereditary disorder, is characterized by deficient development of multiple ectodermal structures including hair, sweat glands and teeth. If caused by mutations in the genes EDA, EDA1R or EDARADD, phenotypes are often very similar as the result of a common signaling pathway. Single-nucleotide polymorphisms (SNPs) affecting any gene product in this pathway may cause inter- and intrafamilial variability. In a cohort of 124 HED patients, genotyping was attempted by Sanger sequencing of EDA, EDA1R, EDARADD, TRAF6 and EDA2R and by multiplex ligation-dependent probe amplification (MLPA). Pathogenic mutations were detected in 101 subjects with HED, affecting EDA, EDA1R and EDARADD in 88%, 9% and 3% of the cases, respectively, and including 23 novel mutations. MLPA revealed exon copy-number variations in five unrelated HED families (two deletions and three duplications). In four of them, the genomic breakpoints could be localized. The EDA1R variant rs3827760 (p.Val370Ala), known to lessen HED-related symptoms, was found only in a single individual of Asian origin, but in none of the 123 European patients. Another SNP, rs1385699 (p.Arg57Lys) in EDA2R, however, appeared to have some impact on the hair phenotype of European subjects with EDA mutations.

show abstract

“…TRAF6 transduces signals from RANKL-RANK interactions resulting in NF-kB activation. Osteopetrosis due to mutations or deletions in TRAF6 has not been previously reported in humans; a short deletion in the last exon of TRAF6 was implicated in one case of hypohidrotic ectodermal dysplasia (17,18). Osteoclasts were generated from splenocytes of Traf6 KO mice following stimulation with macrophage colony-stimulating factor and transforming growth factor-beta, suggesting that in the absence of TRAF6 osteoclast development can progress by alternative or redundant pathways; however, the osteoclasts generated in this model exhibit impaired function (3).…”

Section: Discussionmentioning

confidence: 99%

Homozygous deletion of RAG1, RAG2 and 5′ region TRAF6 causes severe immune suppression and atypical osteopetrosis

et al. 2017

View full text Add to dashboard Cite

Mutations of several genes have been implicated in autosomal recessive osteopetrosis (OP), a disease caused by impaired function and differentiation of osteoclasts. Severe combined immune deficiencies (SCID) can likewise result from different genetic mutations. We report two siblings with SCID and an atypical phenotype of OP. A biallelic microdeletion encompassing the 5' region of TRAF6, RAG1 and RAG2 genes was identified. TRAF6, a tumor necrosis factor receptor-associated family member, plays an important role in T cell signaling and in RANKL-dependent osteoclast differentiation and activation but its role in human OP has not been previously reported. The RAG proteins are essential for recombination of B and T cell receptors, and for the survival and differentiation of these cells. This is the first study to report a homozygous deletion of TRAF6 as a cause of human disease.

show abstract

A new mutation resulting in the truncation of the TRAF6-interacting domain of XEDAR: a possible novel cause of hypohidrotic ectodermal dysplasia: Figure 1

Cited by 23 publications

References 8 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

Mutational spectrum in 101 patients with hypohidrotic ectodermal dysplasia and breakpoint mapping in independent cases of rare genomic rearrangements

Homozygous deletion of RAG1, RAG2 and 5′ region TRAF6 causes severe immune suppression and atypical osteopetrosis

Contact Info

Product

Resources

About