Severe Cenani-Lenz syndrome caused by loss of LRP4 function

• Published in: American journal of medical genetics. Part A Vol. 161A; no. 6; pp. 1475 - 1479
• Main Authors: Kariminejad, Ariana, Stollfuß, Barbara, Li, Yun, Bögershausen, Nina, Boss, Karin, Hennekam, Raoul C.M., Wollnik, Bernd
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-06-2013; Wiley Subscription Services, Inc
• Subjects: Abnormalities, Multiple - diagnosis; Abnormalities, Multiple - genetics; Cenani-Lenz syndrome; Codon, Nonsense; Embryos; Genetic Association Studies; Homozygote; Humans; Infant; LDL-Receptor Related Proteins - genetics; LDL-Receptor Related Proteins - metabolism; Limb Deformities, Congenital - diagnosis; Limb Deformities, Congenital - genetics; limb development; LRP4; Male; oligodactyly; Pedigree; Phenotype; Sequence Analysis, DNA; Signal Transduction; syndactyly; Syndactyly - diagnosis; Syndactyly - genetics
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.35920

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. © 2013 Wiley Periodicals, Inc.