PUBLICATION
Expanding the genotypic spectrum of CCBE1 mutations in Hennekam syndrome
- Authors
- Crawford, J., Bower, N.I., Hogan, B.M., Taft, R.J., Gabbett, M.T., McGaughran, J., Simons, C.
- ID
- ZDB-PUB-160628-4
- Date
- 2016
- Source
- American journal of medical genetics. Part A 170(10): 2694-7 (Journal)
- Registered Authors
- Hogan, Ben M.
- Keywords
- CCBE1, Hennekam syndrome, exome sequencing, lymphedema
- MeSH Terms
-
- Alleles
- Amino Acid Sequence
- Animals
- Calcium-Binding Proteins/genetics*
- Cell Line
- Craniofacial Abnormalities/diagnosis*
- Craniofacial Abnormalities/genetics*
- Gene Expression
- Gene Frequency
- Genotype*
- Humans
- Infant, Newborn
- Lymphangiectasis, Intestinal/diagnosis*
- Lymphangiectasis, Intestinal/genetics*
- Lymphedema/diagnosis*
- Lymphedema/genetics*
- Male
- Mutation*
- Polymorphism, Single Nucleotide
- Sequence Analysis, DNA
- Tumor Suppressor Proteins/genetics*
- Zebrafish
- PubMed
- 27345729 Full text @ Am. J. Med. Genet. A
Citation
Crawford, J., Bower, N.I., Hogan, B.M., Taft, R.J., Gabbett, M.T., McGaughran, J., Simons, C. (2016) Expanding the genotypic spectrum of CCBE1 mutations in Hennekam syndrome. American journal of medical genetics. Part A. 170(10):2694-7.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping