p63 Gene mutations in EEC syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation

Van Bokhoven, Hans, Hamel, Ben C. J., Bamshad, Mike, Sangiorgi, Eugenio, Gurrieri, Fiorella, Duijf, Pascal H. G., Vanmolkot, Kaate R. J., van Beusekom, Ellen, van Beersum, Sylvia E. C., Celli, Jacopo, Merkx, Gerard F. M., Tenconi, Romano, Fryns, Jean Pierre, Verloes, Alain, Newbury-Ecob, Ruth A., Raas-Rotschild, Annick, Majewski, Frank, Beemer, Frits A., Janecke, Andreas, Chitayat, David, Crisponi, Giangiorgio, Kayserili, Hülya, Yates, John R. W., Neri, Giovanni and Brunner, Han G. (2001) p63 Gene mutations in EEC syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation. American Journal of Human Genetics, 36 3: 481-492. doi:10.1086/323123


Author Van Bokhoven, Hans
Hamel, Ben C. J.
Bamshad, Mike
Sangiorgi, Eugenio
Gurrieri, Fiorella
Duijf, Pascal H. G.
Vanmolkot, Kaate R. J.
van Beusekom, Ellen
van Beersum, Sylvia E. C.
Celli, Jacopo
Merkx, Gerard F. M.
Tenconi, Romano
Fryns, Jean Pierre
Verloes, Alain
Newbury-Ecob, Ruth A.
Raas-Rotschild, Annick
Majewski, Frank
Beemer, Frits A.
Janecke, Andreas
Chitayat, David
Crisponi, Giangiorgio
Kayserili, Hülya
Yates, John R. W.
Neri, Giovanni
Brunner, Han G.
Title p63 Gene mutations in EEC syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation
Formatted title
p63 Gene mutations in EEC syndrome, limb-mammary syndrome, and isolated split hand–split foot malformation suggest a genotype-phenotype correlation
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
Publication date 2001-07-01
Sub-type Article (original research)
DOI 10.1086/323123
Volume 36
Issue 3
Start page 481
End page 492
Total pages 12
Language eng
Formatted abstract
p63 mutations have been associated with EEC syndrome (ectrodactyly, ectodermal dysplasia, and cleft lip/palate), as well as with nonsyndromic split hand–split foot malformation (SHFM). We performed p63 mutation analysis in a sample of 43 individuals and families affected with EEC syndrome, in 35 individuals affected with SHFM, and in three families with the EEC-like condition limb-mammary syndrome (LMS), which is characterized by ectrodactyly, cleft palate, and mammary-gland abnormalities. The results differed for these three conditions. p63 gene mutations were detected in almost all (40/43) individuals affected with EEC syndrome. Apart from a frameshift mutation in exon 13, all other EEC mutations were missense, predominantly involving codons 204, 227, 279, 280, and 304. In contrast, p63 mutations were detected in only a small proportion (4/35) of patients with isolated SHFM. p63 mutations in SHFM included three novel mutations: a missense mutation (K193E), a nonsense mutation (Q634X), and a mutation in the 3′ splice site for exon 5. The fourth SHFM mutation (R280H) in this series was also found in a patient with classical EEC syndrome, suggesting partial overlap between the EEC and SHFM mutational spectra. The original family with LMS (van Bokhoven et al. 1999) had no detectable p63 mutation, although it clearly localizes to the p63 locus in 3q27. In two other small kindreds affected with LMS, frameshift mutations were detected in exons 13 and 14, respectively. The combined data show that p63 is the major gene for EEC syndrome, and that it makes a modest contribution to SHFM. There appears to be a genotype-phenotype correlation, in that there is a specific pattern of missense mutations in EEC syndrome that are not generally found in SHFM or LMS.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 212 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 237 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 06 Dec 2013, 01:30:54 EST by Pascal Duijf on behalf of UQ Diamantina Institute