Pulleyn L J, Winter R M, Reardon W, McKeown C, Jones B, Hayward R, Evans R, Malcolm S
Molecular Genetics Unit, Institute of Child Health, University College London, UK.
Clin Genet. 1999 Jun;55(6):473-7. doi: 10.1034/j.1399-0004.1999.550613.x.
Craniofrontonasal dysplasia (CFND) is a rare X-linked disorder that maps to a 13-cM region on Xp22. Phenotypic features include craniosynostosis, hypertelorism and a broad nasal root with or without a bifid nasal tip. Multiple examples have been reported of males having a less severe phenotype than females. We report haplotype analyses in two CFND families over the critical region to which the gene has been mapped. In pedigree 1, a clinically unaffected male inherited the affected marker haplotype spanning the critical region. We suggest that this individual does have the CFND mutation, but has an extremely mild phenotype that is not detectable with clinical examination. Under the assumption that he is an unknown phenotype, a combined two-point LOD score of 1.68 at zero recombination was obtained, increasing the previously reported total to 5.61 (DXS8022). The data do not narrow down the critical region. This result stresses the importance of subjecting fathers of apparently sporadic cases to a highly critical medical examination and may also explain the unequal ratio of reported female-to-male cases.
颅额鼻发育不良（CFND）是一种罕见的X连锁疾病，定位于Xp22上一个13厘摩的区域。其表型特征包括颅缝早闭、眼距过宽以及宽阔的鼻根，鼻尖可有或无分叉。已有多个例子报道男性的表型比女性轻。我们报告了对两个CFND家系在已确定基因所在的关键区域进行的单倍型分析。在系谱1中，一名临床无症状的男性继承了跨越关键区域的受累标记单倍型。我们认为该个体确实携带CFND突变，但具有极其轻微的表型，临床检查无法检测到。假设他是未知表型，在零重组时两点LOD得分合并为1.68，使先前报道的总数增加到5.61（DXS8022）。这些数据并未缩小关键区域。这一结果强调了对明显散发病例的父亲进行严格医学检查的重要性，也可能解释了所报道的女性与男性病例比例不均的现象。
