Vertical transmission of a frontonasal phenotype caused by a novel ALX4 mutation
Vertical transmission of a frontonasal phenotype caused by a novel ALX4 mutation
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DOI：
10.1002/ajmg.a.35762
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发表时间：
2013-03-01
影响因子：
2
通讯作者：
Passos-Bueno, Maria Rita
中科院分区：
文献类型：
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作者：
Bertola, Debora R.;Rodrigues, Melina G.;Passos-Bueno, Maria Rita
额鼻发育不良(FND)包括一系列由面部正中发育异常引起的疾病。其病因仍然知之甚少，但最近额鼻发育不良表型与ALX同源框基因家族的功能丧失突变有关，该家族包括ALX1、ALX3和ALX4基因。到目前为止，所有与ALX相关的额鼻表型都符合常染色体隐性遗传模式。相反，ALX4杂合性功能丧失突变只与矢状缝和板状缝交界处孤立的对称性顶骨骨化缺陷有关，称为扩大的顶孔。我们报告了一个由ALX4基因突变(c.1080-1089_delGACCCGGTGCinsCTAAGATCTCAACAGAGATGGCAACT，p.Asp326fsX21引起的母子垂直遗传的轻度额鼻发育不良表型。这是首次报道与ALX4杂合突变相关的额鼻表型。据预测，这种突变会导致蛋白质C-末端区域的无干旱结构域丢失，并保留同源结构域。我们推测，一个不同的机制，一种显性-负性效应，是导致该家族不同表型的原因。(C)2013年威利期刊公司。
Frontonasal dysplasias (FND) comprise a spectrum of disorders caused by abnormal median facial development. Its etiology is still poorly understood but recently frontonasal dysplasia phenotypes were linked to loss-of-function mutations in the ALX homeobox gene family, which comprises the ALX1, ALX3, and ALX4 genes. All ALX-related frontonasal phenotypes till date had been compatible with an autosomal recessive mode of inheritance. In contrast, heterozygous loss-of-function mutations in ALX4 had been only associated with isolated symmetrical parietal ossification defects at the intersection of the sagittal and lambdoid sutures, known as enlarged parietal foramina. We report a family with vertical transmission from mother to son of mild frontonasal dysplasia phenotype caused by a novel ALX4 gene mutation (c.1080-1089_delGACCCGGTGCinsCTAAGATCTCAACAGAGATGGCAACT, p.Asp326fsX21).This is the first report of a frontonasal phenotype related to a heterozygous mutation in ALX4. This mutation is predicted to cause the loss of the aristaless domain in the C-terminal region of the protein and preserves the homeodomain. We speculate that a different mechanism, a dominant-negative effect, is responsible for the distinct phenotype in this family. (c) 2013 Wiley Periodicals, Inc.