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Increasing evidence of hereditary lymphedema caused by CELSR1 loss‐of‐function variants
Author(s) -
Maltese Paolo E.,
Michelini Sandro,
Ricci Maurizio,
Maitz Silvia,
Fiorentino Alessandro,
Serrani Roberta,
Lazzerotti Alessandra,
Bruson Alice,
Paolacci Stefano,
Benedetti Sabrina,
Bertelli Matteo
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61269
Subject(s) - penetrance , lymphedema , proband , biology , loss function , genetics , exome sequencing , polygene , phenotype , gene , mutation , quantitative trait locus , cancer , breast cancer
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.