Pattern of <i>p63</i> mutations and their phenotypes—update

Rinne, Tuula; Hamel, B.C.J.; Bokhoven, Hans van; Brunner, Han G.

doi:10.1002/ajmg.a.31271

Cited by 146 publications

(204 citation statements)

References 41 publications

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“…4 In humans, several syndromes showing abnormalities in limbs, skin and epithelial annexes are caused by mutations in the p63 gene. 5 p63 is crucial for the activation of the epithelial cell adhesion programme. 6 Recently, p63 has been demonstrated to play a major role in maintaining the proliferative potential of stem cells of the multilayered epithelia.…”

mentioning

confidence: 99%

p63 regulates the caspase-8-FLIP apoptotic pathway in epidermis

et al. 2008

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The transcription factor p63, member of the p53 family, is crucial for epithelial development. An RNAi screening identified the apoptotic gene Procaspase-8 as a target activated by p63. The caspase-8 inhibitor FLIP is also under p63 control. We analysed and detailed the direct transactivation through the use of RNAi, reporter assays, ChIPs, western blots, confocal studies in HaCat, as well as in primary human keratinocytes. The direct DNp63 regulation of these targets was confirmed in vivo using transgenic DNp63 mice under the K5 promoter, as compared with p63 knockout mice, and in vitro in normal human primary keratinocytes following UV irradiation. Lowering the steady state of p63 protein levels changes the relative ratio of FLIP isoforms, causing the activation of the expressed, inactive Procaspase-8, into the active isoform thus triggering the proapoptotic cascade. Therefore, p63 fine-tunes the Procaspase-8-FLIP pro-and antiapoptotic pathway in keratinocytes.

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confidence: 99%

p63 regulates the caspase-8-FLIP apoptotic pathway in epidermis

et al. 2008

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“…Mutation analysis of the P63 exons previously implicated in SHFM4 20,21 (exons 5-8, 13, and 14) was carried out as part of an initial clinical diagnostic workup and no sequence alterations were detected in the proband. The proband was analysed with the 500K Affymetrix array and individual S108 ( .…”

Section: Familymentioning

confidence: 99%

17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD)

Armour

Bulman

Jarinova³

et al. 2011

Eur J Hum Genet

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Split-hand/foot malformation with long-bone deficiency (SHFLD) is a relatively rare autosomal-dominant skeletal disorder, characterized by variable expressivity and incomplete penetrance. Although several chromosomal loci for SHFLD have been identified, the molecular basis and pathogenesis of most SHFLD cases are unknown. In this study we describe three unrelated kindreds, in which SHFLD segregated with distinct but overlapping duplications in 17p13.3, a region previously linked to SHFLD. In a large three-generation family, the disorder was found to segregate with a 254 kb microduplication; a second microduplication of 527 kb was identified in an affected female and her unaffected mother, and a 430 kb microduplication versus microtriplication was identified in three affected members of a multi-generational family. These findings, along with previously published data, suggest that one locus responsible for this form of SHFLD is located within a 173 kb overlapping critical region, and that the copy gains are incompletely penetrant.

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“…Mammary gland hypoplasia and nipple hypoplasia are frequent findings in limb mammary syndrome (LMS, OMIM 603543) and in acro-dermatoungual-lacrimal-tooth syndrome (ADULT, OMIM 103285) but are rare in other p63-related conditions. 1 ADULT syndrome is further distinguished from other p63 syndromes by absence of orofacial clefting and by prominent ectodermal signs. Abnormal hair or skin abnormalities have not been reported among LMS patients.…”

Section: Introductionmentioning

confidence: 99%

Delineation of the ADULT syndrome phenotype due to arginine 298 mutations of the p63 gene

et al. 2006

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The ADULT syndrome (Acro-Dermato-Ungual-Lacrimal-Tooth, OMIM 103285) is a rare ectodermal dysplasia associated with limb malformations and caused by heterozygous mutations in p63. ADULT syndrome has clinical overlap with other p63 mutation syndromes, such as EEC (OMIM 604292), LMS (OMIM 603543), AEC (106260), RHS (129400) and SHFM4 (605289). ADULT syndrome characteristics are ectrodactyly, ectodermal dysplasia, mammary gland hypoplasia and normal lip and palate. The latter findings allow differentiation from EEC syndrome. LMS differs by milder ectodermal involvement. Here, we report three new unrelated ADULT syndrome families, all with mutations of arginine 298. On basis of 16 patients in five families with R298 mutation, we delineate the ADULT syndrome phenotype. In addition, we have documented a gain-of-function effect on the dNp63gamma isoform caused by this mutation. We discuss the possible relevance of oral squamous cell carcinoma in one patient, who carries this p63 germline mutation.

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Pattern of p63 mutations and their phenotypes—update

Cited by 146 publications

References 41 publications

p63 regulates the caspase-8-FLIP apoptotic pathway in epidermis

p63 regulates the caspase-8-FLIP apoptotic pathway in epidermis

17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD)

Delineation of the ADULT syndrome phenotype due to arginine 298 mutations of the p63 gene

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