Evidence for pseudodominant inheritance of atrichia with papular lesions.
Evidence for pseudodominant inheritance of atrichia with papular lesions.
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DOI：
10.1046/j.1523-1747.2002.01740.x
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发表时间：
2002-05
期刊：
影响因子：
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通讯作者：
A. Zlotogorski;A. Martinez-Mir;Jack Green;HaMut Lamdagger;Andrei A Panteleyevdagger;R. Sinclair;A. Christiano
中科院分区：
文献类型：
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作者：
A. Zlotogorski;A. Martinez-Mir;Jack Green;HaMut Lamdagger;Andrei A Panteleyevdagger;R. Sinclair;A. Christiano
无毛丘疹病变是一种罕见的形式的全秃，其中突变的无毛基因已被证明是潜在的表型。在迄今为止的文献中，非丘疹与丘疹病变通常被报道为常染色体隐性遗传方式。少数罕见的情况下存在，然而，其中父母到孩子的传播与丘疹病变已被记录。在本研究中，通过寻找人类无毛基因的突变，进一步研究了一个母子传播家族中无毛病伴丘疹病变的分子基础。具体来说，我们想确定这个病例是否真的代表了一个显性遗传的非丘疹病变的例子，或者是否另一种遗传模式可能是导致该亲属疾病的原因。例如，当一个已知隐性遗传病的个体有一个临床未受影响的伴侣，但意外地生下了与患病父母患有相同隐性遗传病的孩子时，就会发生假显性遗传。通过分子诊断和单倍型分析，这种遗传很容易与经典显性遗传区分开来。在这里报道的这个家庭中，我们已经确定母亲和儿子实际上都是无毛基因R33X的一种新突变的纯合子。我们为无毛丘疹病的假显性遗传提供了第一个证据，同时扩展了我们对人类无毛基因致病突变的认识。重要的是，这一信息允许对家族中个体传播风险的遗传咨询进行修订，以前不可能在不了解这种不寻常的亲属中非丘疹病变的遗传基础的情况下进行遗传咨询。
Atrichia with papular lesions is a rare form of total alopecia, in which mutations in the hairless gene have been shown to underlie the phenotype. In the literature to date, atrichia with papular lesions has generally been reported to be inherited in an autosomal recessive manner. A few rare cases exist, however, in which parent-to-child transmission of atrichia with papular lesions has been documented. In this study, further investigations were carried out into the molecular basis of atrichia with papular lesions in a family with mother-to-son transmission by searching for mutations in the human hairless gene. Specific ally, we wanted to determine whether this case truly represented an example of dominantly inherited atrichia with papular lesions, or whether another mode of inheritance might be responsible for the disorder in this kindred. Pseudodominant inheritance, for example, occurs when an individual with a known recessive disorder has a clinically unaffected partner, but then unexpectedly gives birth to children who are affected with the same recessive disorder as the affected parent, and can easily be distinguished from classical dominant inheritance with molecular diagnosis and haplotype analysis. In the family reported here, we have determined that both the mother and son are, in fact, homozygous for a novel mutation in the hairless gene, R33X. We provide the first evidence for pseudodominant inheritance in atrichia with papular lesions, and at the same time extend our knowledge of pathogenetic mutations in the human hairless gene. Importantly, this information allows revisions in genetic counseling for risk of transmission for individuals in the family, previously impossible in the absence of knowing the genetic basis of atrichia with papular lesions in this unusual kindred.