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
Department of Cell and Molecular Pathology, St John's Institute of Dermatology, The Guy's, King's College and St Thomas' Hospitals' Medical School, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK.
Br J Dermatol. 2002 Feb;146(2):216-20. doi: 10.1046/j.1365-2133.2002.04638.x.
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 (Ectrodactyly, Ectodermal dysplasia, Clefting) syndrome.
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.
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 AciI site on mutant allele) were used for DNA-based prenatal diagnosis.
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.
These data expand the p63 gene mutation database and provide the first example of a DNA-based prenatal test in this ectodermal dysplasia syndrome.
p63基因DNA结合域的种系错义突变最近已被确定为常染色体显性EEC（缺指（趾）、外胚层发育不良、腭裂）综合征的分子基础。
检测一名36岁女性、她58岁的父亲和她11岁儿子（均患有EEC综合征）的基因组DNA，以确定内在的p63突变，并在遗传咨询后，利用该突变知识对后续妊娠进行基于DNA的孕早期产前诊断。
从绒毛膜绒毛中提取胎儿DNA，并用于扩增含有潜在突变的p63基因第7外显子。基于DNA的产前诊断采用直接测序和限制性内切酶消化（突变等位基因上AciI位点缺失）。
我们在所有三名受影响个体中鉴定出杂合的精氨酸到组氨酸p63突变，即R279H。产前诊断显示纯合野生型序列，预测胎儿未受影响：随后一名健康男婴足月出生。
这些数据扩展了p63基因突变数据库，并提供了该外胚层发育不良综合征基于DNA的产前检测的首个实例。
