Abstract：
Wiedemann-Rautenstrauch syndrome, also known as neonatal progeroid syndrome, is a rare condition with fewer than 40 patients reported in the literature. Characteristic physical findings include neonatal progeroid appearance, sparse scalp hair, prominent scalp veins, and lipoatrophy; in addition, neonatal teeth are often a distinctive finding. The inheritance pattern of this disorder has been postulated to be autosomal recessive, although a specific gene has not been identified. Here we report an infant with the characteristic phenotypic features of Wiedemann-Rautenstrauch syndrome in whom exome sequencing identified two pathogenic variants in POLR3A: c.1909+18G>A; p.(Y637Cfs*23) and c.2617C>T; p.(R873*). Mutations in POLR3A (OMIM #614258) are associated with 4H leukodystrophy syndrome characterized by the triad of hypomyelination, hypodontia, and hypogonadotrophic hypogonadism. The present patient\'s genotype implies a broader phenotypic range for POLR3A mutations and might expand the clinical spectrum. This proband is notable because she had two null pathogenic variants. Replication in other patients clinically diagnosed with Wiedemann-Rautenstrauch syndrome is needed to further demonstrate this gene-disease association. © 2016 Wiley Periodicals, Inc.
摘要：
Wiedemann-Rautenstauch综合征,也被称为新生儿孕激素综合征，是一种罕见的疾病，文献中报道的患者少于40例。特征性的体格检查结果包括新生儿早衰样外观，稀疏的头皮头发，突出的头皮静脉，和脂肪萎缩；此外，新生儿的牙齿通常是一个独特的发现。这种疾病的遗传模式被认为是常染色体隐性遗传，尽管尚未鉴定出特定的基因。在这里，我们报告了一个具有Wiedemann-Rautenstrauch综合征特征性表型特征的婴儿，其中外显子组测序在POLR3A中鉴定出两种致病性变异：c.190918G>A;p。（Y637Cfs*23）和c.2617C>T;p。（R873*）。POLR3A（OMIM#614258）的突变与4H脑白质营养不良综合征相关，其特征是髓鞘不足三联症，缺省症,和低促性腺激素性性腺功能减退.本患者的基因型意味着POLR3A突变的表型范围更广，并可能扩大临床范围。这个先证者是值得注意的，因为她有两个无效的致病变体。需要在临床诊断为Wiedemann-Rautenstrauch综合征的其他患者中复制，以进一步证明这种基因-疾病关联。©2016威利期刊，Inc.
