Kariminejad Ariana, Stollfuß Barbara, Li Yun, Bögershausen Nina, Boss Karin, Hennekam Raoul C M, Wollnik Bernd
Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
Am J Med Genet A. 2013 Jun;161A(6):1475-9. doi: 10.1002/ajmg.a.35920. Epub 2013 May 1.
Limb patterning and growth are complex embryonic processes in which the elaborately orchestrated interplay of diverse endocrine and paracrine factors is crucial to limb integrity. LRP4 is a lipoprotein receptor known for its regulatory effects on LRP5- and LRP6-mediated Wnt signaling, a pathway that plays a pivotal role in limb development. Recessive mutations in LRP4 have been shown to cause Cenani-Lenz syndrome, which is characterized by severe limb malformations, an unusual face, and renal abnormalities. We report on a child with severe Cenani-Lenz syndrome caused by a novel homozygous nonsense mutation in LRP4. The severity of the phenotype in a patient with absent residual LRP4 function may point to a genotype-phenotype correlation.
肢体模式形成和生长是复杂的胚胎过程，在这个过程中，多种内分泌和旁分泌因子精心协调的相互作用对于肢体完整性至关重要。LRP4是一种脂蛋白受体，因其对LRP5和LRP6介导的Wnt信号通路的调节作用而闻名，该信号通路在肢体发育中起关键作用。已证明LRP4中的隐性突变会导致塞纳尼-伦茨综合征，其特征为严重的肢体畸形、特殊面容和肾脏异常。我们报告了一名因LRP4中一个新的纯合无义突变导致严重塞纳尼-伦茨综合征的儿童。在没有残余LRP4功能的患者中，表型的严重程度可能表明存在基因型-表型相关性。
