title: Expanding the genotypic spectrum of CCBE1 mutations in Hennekam syndrome.
abstract: 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.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Joanna
authors.initials: J
authors.lastname: Crawford
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Neil I
authors.initials: NI
authors.lastname: Bower
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Hogan
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.|Illumina, Inc., San Diego, California.|School of Medicine and Health, The George Washington University, Washington, District of Columbia.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Taft
authors.affiliation: Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia.|School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Gabbett
authors.affiliation: Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia. julie.mcgaughran@health.qld.gov.au.|School of Medicine, The University of Queensland, Brisbane, Queensland, Australia. julie.mcgaughran@health.qld.gov.au.
authors.forename: Julie
authors.initials: J
authors.lastname: McGaughran
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Cas
authors.initials: C
authors.lastname: Simons
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002460:Cell Line; D019465:Craniofacial Abnormalities / Q000175:diagnosis* / Q000235:genetics*; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008201:Lymphangiectasis, Intestinal / Q000175:diagnosis* / Q000235:genetics*; D008209:Lymphedema / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D015027:Zebrafish
chemical_list: C546964:CCBE1 protein, human; D002135:Calcium-Binding Proteins; D025521:Tumor Suppressor Proteins
keywords: CCBE1; Hennekam syndrome; exome sequencing; lymphedema