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Expanding the genotypic spectrum of CCBE1 mutations in Hennekam syndrome
Author(s) -
Crawford Joanna,
Bower Neil I.,
Hogan Benjamin M.,
Taft Ryan J.,
Gabbett Michael T.,
McGaughran Julie,
Simons Cas
Publication year - 2016
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.37803
Subject(s) - genotype , genetics , spectrum (functional analysis) , mutation , biology , broad spectrum , gene , physics , chemistry , quantum mechanics , combinatorial chemistry
Hennekam lymphangiectasia–lymphedema syndrome is an autosomal recessive disorder, with 25% of patients having mutations in CCBE1 . We identified a family with two brothers presenting with primary lymphedema, and performed exome sequencing to determine the cause of their disease. Analysis of four family members showed that both affected brothers had the same rare compound heterozygous mutations in CCBE1 . The presumed paternally inherited NM_133459.3:c.310G>A; p.(Asp104Asn), lies adjacent to other known pathogenic CCBE1 mutations, while the maternally inherited NM_133459.3:c.80T>C; p.(Leu27Pro) lies in the CCBE1 signal peptide, which has not previously been associated with disease. Functional analysis in a zebrafish model of lymphatic disease showed that both mutations lead to CCBE1 loss of function, confirming the pathogenicity of these variants and expanding the genotypic spectrum of lymphatic disorders. © 2016 Wiley Periodicals, Inc.