Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome
- PMID: 10535733
- DOI: 10.1016/s0092-8674(00)81646-3
Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome
Abstract
EEC syndrome is an autosomal dominant disorder characterized by ectrodactyly, ectodermal dysplasia, and facial clefts. We have mapped the genetic defect in several EEC syndrome families to a region of chromosome 3q27 previously implicated in the EEC-like disorder, limb mammary syndrome (LMS). Analysis of the p63 gene, a homolog of p53 located in the critical LMS/EEC interval, revealed heterozygous mutations in nine unrelated EEC families. Eight mutations result in amino acid substitutions that are predicted to abolish the DNA binding capacity of p63. The ninth is a frameshift mutation that affects the p63alpha, but not p63beta and p63gamma isotypes. Transactivation studies with these mutant p63 isotypes provide a molecular explanation for the dominant character of p63 mutations in EEC syndrome.
Similar articles
-
p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation.Am J Hum Genet. 2001 Sep;69(3):481-92. doi: 10.1086/323123. Epub 2001 Jul 17. Am J Hum Genet. 2001. PMID: 11462173 Free PMC article.
-
Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63.Hum Mol Genet. 2001 Feb 1;10(3):221-9. doi: 10.1093/hmg/10.3.221. Hum Mol Genet. 2001. PMID: 11159940
-
Split-hand/split-foot malformation is caused by mutations in the p63 gene on 3q27.Am J Hum Genet. 2000 Jul;67(1):59-66. doi: 10.1086/302972. Epub 2000 Jun 5. Am J Hum Genet. 2000. PMID: 10839977 Free PMC article.
-
The p63 gene in EEC and other syndromes.J Med Genet. 2002 Jun;39(6):377-81. doi: 10.1136/jmg.39.6.377. J Med Genet. 2002. PMID: 12070241 Free PMC article. Review.
-
P63 gene mutations and human developmental syndromes.Am J Med Genet. 2002 Oct 15;112(3):284-90. doi: 10.1002/ajmg.10778. Am J Med Genet. 2002. PMID: 12357472 Review.
Cited by
-
Case report: Artificial thymic organoids facilitate clinical decisions for a patient with a TP63 variant and severe persistent T cell lymphopenia.Front Immunol. 2024 Sep 18;15:1438383. doi: 10.3389/fimmu.2024.1438383. eCollection 2024. Front Immunol. 2024. PMID: 39364398 Free PMC article.
-
P63 regulates tubular formation via epithelial-to-mesenchymal transition.Oncogene. 2014 Mar 20;33(12):1548-57. doi: 10.1038/onc.2013.101. Epub 2013 Apr 1. Oncogene. 2014. PMID: 23542170 Free PMC article.
-
An allelic series of Trp63 mutations defines TAp63 as a modifier of EEC syndrome.Am J Med Genet A. 2013 Aug;161A(8):1961-71. doi: 10.1002/ajmg.a.36074. Epub 2013 Jun 14. Am J Med Genet A. 2013. PMID: 23775923 Free PMC article.
-
p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation.Am J Hum Genet. 2001 Sep;69(3):481-92. doi: 10.1086/323123. Epub 2001 Jul 17. Am J Hum Genet. 2001. PMID: 11462173 Free PMC article.
-
Comprehensive clinical and molecular studies in split-hand/foot malformation: identification of two plausible candidate genes (LRP6 and UBA2).Eur J Hum Genet. 2019 Dec;27(12):1845-1857. doi: 10.1038/s41431-019-0473-7. Epub 2019 Jul 22. Eur J Hum Genet. 2019. PMID: 31332306 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases
Research Materials
Miscellaneous
