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EEC ( E ctrodactyly, E ctodermal dysplasia, C lefting) syndrome: heterozygous mutation in the p63 gene (R279H) and DNA‐based prenatal diagnosis
Author(s) -
South A.P.,
Ashton G.H.S.,
Willoughby C.,
Ellis I.H.,
Bleck O.,
Hamada T.,
Mannion G.,
Wessagowit V.,
Hashimoto T.,
Eady R.A.J.,
Mcgrath J.A.
Publication year - 2002
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1046/j.1365-2133.2002.04638.x
Subject(s) - ectrodactyly , genetics , ectodermal dysplasia , prenatal diagnosis , mutation , exon , biology , medicine , gene , fetus , pregnancy
Summary Background Germline mis‐sense mutations in the DNA‐binding domain of the p63 gene have recently been established as the molecular basis for the autosomal dominant EEC ( E ctrodactyly, E ctodermal dysplasia, C lefting) syndrome. Objectives To examine genomic DNA from a 36‐year‐old woman, her 58‐year‐old father and her 11‐year‐old son, all with the EEC syndrome, to determine the inherent p63 mutation and, after genetic counselling, to use knowledge of the mutation to undertake a first‐trimester DNA‐based prenatal diagnosis in a subsequent pregnancy. Methods Fetal DNA was extracted from chorionic villi and used to amplify exon 7 of p63 containing the potential mutation. Direct sequencing and restriction endonuclease digestion (loss of Aci I site on mutant allele) were used for DNA‐based prenatal diagnosis. Results We identified a heterozygous arginine to histidine p63 mutation, R279H, in all three affected individuals. Prenatal diagnosis demonstrated a homozygous wild‐type sequence predicting an unaffected child: a healthy boy was subsequently born at full‐term. Conclusions These data expand the p63 gene mutation database and provide the first example of a DNA‐based prenatal test in this ectodermal dysplasia syndrome.