2. Academic Validation
  3. Increasing evidence of hereditary lymphedema caused by CELSR1 loss-of-function variants

Increasing evidence of hereditary lymphedema caused by CELSR1 loss-of-function variants

  • Am J Med Genet A. 2019 Sep;179(9):1718-1724. doi: 10.1002/ajmg.a.61269.
Paolo E Maltese 1,  Sandro Michelini 2,  Maurizio Ricci 3,  Silvia Maitz 4,  Alessandro Fiorentino 2,  Roberta Serrani 3,  Alessandra Lazzerotti 4,  Alice Bruson 1,  Stefano Paolacci 1,  Sabrina Benedetti 1,  Matteo Bertelli 1
Affiliations

Affiliations

  • 1 MAGI's Lab, Rovereto, Italy.
  • 2 Rehabilitation Department, San Giovanni Battista Hospital, Rome, Italy.
  • 3 Division of Rehabilitation Medicine, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Italy.
  • 4 Clinical Pediatric Genetics Unit, Pediatrics Clinic, Fondazione MBBM, San Gerardo Hospital, Monza, Italy.
PMID: 31215153 DOI: 10.1002/ajmg.a.61269
Abstract

A whole exome sequencing approach was recently used to detect a CELSR1 truncating variant associated with lymphedema in a large pedigree. Since this first report, no other similar associations have been reported in the literature. Here, we present the genetic results of 95 probands tested using a next generation sequencing panel that covered all known lymphedema-associated genes, including CELSR1. Five out of 95 probands (5.3%) were found to carry novel loss-of-function variants in CELSR1. Family segregation studies were possible in four out of five probands and showed possible sex-specific differences: CELSR1 variants showed almost complete penetrance in females and were associated with early-onset lymphedema, whereas in males they showed incomplete penetrance and were associated with late onset of the condition. Since the percentage of lymphedema patients carrying CELSR1 variants is not negligible, we do not hesitate to recommend including this gene in routine genetic testing.

Keywords

CELSR1; Noonan syndrome; lymphedema; next generation sequencing.

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