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Short report
A novel stop mutation in the vascular endothelial growth factor-C gene (VEGFC) results in Milroy-like disease
  1. Emilia Balboa-Beltran1,
  2. María J Fernández-Seara2,
  3. Alejandro Pérez-Muñuzuri2,
  4. Ramón Lago1,
  5. Carlos García-Magán2,
  6. María L Couce2,
  7. Beatriz Sobrino3,
  8. Jorge Amigo3,
  9. Angel Carracedo1,3,4,
  10. Francisco Barros1,3
  1. 1Fundación Pública Galega de Medicina Xenómica, SERGAS, Santiago de Compostela, Spain
  2. 2Servicio de Neonatología, Departamento de Pediatría, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
  3. 3Grupo de Medicina Xenómica-USC, CIBERER, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain
  4. 4King Abdulaziz University, Center of Excellence in Genomic Medicine Research, Jeddah, Saudi Arabia
  1. Correspondence to Dr Francisco Barros, Fundación Pública Galega de Medicina Xenómica, Edf. Consultas planta-2, Hospital Clinico Universitario, Santiago de Compostela 15707, Spain; francisco.barros{at}usc.es

Abstract

Background Milroy and Milroy-like disease are rare disorders characterised by congenital lymphoedema caused by dysfunctional lymphatic vessel formation. Loss of extracellular response mediated by vascular endothelial growth factor receptor 3 (VEGFR-3) is associated with Milroy disease, and VEGFR-3 gene is mutated in around 70% of the cases diagnosed. The only genetic alteration known to be associated with Milroy-like disease was recently identified in a family with a frameshift mutation in vascular endothelial growth factor C (VEGFC) gene, which encodes a VEGFR3 ligand.

Methods and results We report a newborn patient with an external phenotype consistent with Milroy disease and a truncating mutation (p.R210X) in the VEGFC gene detected by exome sequence analysis. Subsequent analysis, by lymphoscintigraphic scan, performed for research purposes, allowed us to correct the diagnosis, confirming patient’s disease as Milroy-like. The mutation segregates with the phenotype in the family according to a dominant model with full penetrance.

Conclusions The clinical presentation, similar to Milroy disease, indicates an overlapping of the external phenotype of both diseases, suggesting that genetic analysis of VEGFC would be useful in diagnosing patients that present with Milroy features but have no mutation in VEGFR-3. Establishing a well-defined genetic pattern would help with differential diagnosis.

  • Clinical Genetics
  • Diagnostics
  • Genetic Screening/Counselling

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