Expanding the genotypic spectrum of CCBE1 mutations in Hennekam syndrome

Crawford, Joanna, Bower, Neil I., Hogan, Benjamin M., Taft, Ryan J., Gabbett, Michael T., McGaughran, Julie and Simons, Cas (2016) Expanding the genotypic spectrum of CCBE1 mutations in Hennekam syndrome. American Journal of Medical Genetics, Part A, 170 10: 2694-2697. doi:10.1002/ajmg.a.37803


Author Crawford, Joanna
Bower, Neil I.
Hogan, Benjamin M.
Taft, Ryan J.
Gabbett, Michael T.
McGaughran, Julie
Simons, Cas
Title Expanding the genotypic spectrum of CCBE1 mutations in Hennekam syndrome
Formatted title
Expanding the genotypic spectrum of CCBE1 mutations in Hennekam syndrome
Journal name American Journal of Medical Genetics, Part A   Check publisher's open access policy
ISSN 1552-4833
1552-4825
Publication date 2016-10-01
Year available 2016
Sub-type Article (original research)
DOI 10.1002/ajmg.a.37803
Open Access Status Not yet assessed
Volume 170
Issue 10
Start page 2694
End page 2697
Total pages 4
Place of publication Hoboken, NJ United States
Publisher John Wiley & Sons
Language eng
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. (c) 2016 Wiley Periodicals, Inc.
Formatted 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.
Keyword Hennekam syndrome
Lymphedema
CCBE1
Exome sequencing
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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