ZFIN ID: ZDB-PUB-160628-4
Expanding the genotypic spectrum of CCBE1 mutations in Hennekam syndrome
Crawford, J., Bower, N.I., Hogan, B.M., Taft, R.J., Gabbett, M.T., McGaughran, J., Simons, C.
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
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.