An additional case of Hennekam lymphangiectasia-lymphedema syndrome caused by loss-of-function mutation in ADAMTS3

Am J Med Genet A. 2018 Dec;176(12):2858-2861. doi: 10.1002/ajmg.a.40633. Epub 2018 Nov 18.

Abstract

Hennekam lymphangiectasia-lymphedema syndrome (HKLLS) is a genetically heterogeneous lymphatic dysplasia with characteristic of facial dysmorphism, neurocognitive impairments, and abnormalities of the pericardium, intestinal tract, and extremities. It is an autosomal recessive condition caused by biallelic mutations in CCBE1 (collagen- and calcium-binding epidermal growth factor domain-containing protein 1) (HKLLS1; OMIM 235510) or FAT4 (HKLLS2; OMIM 616006). CCBE1 acts via ADAMTS3 (a disintegrin and metalloprotease with thrombospondin motifs-3 protease) to enhance vascular endothelial growth factor C signaling. There is report of one family supporting mutations in ADAMTS3 as causative for the phenotype labeled as HKLLS3. Here, we report an additional case of HKLLS that appears to be associated with homozygous nonsense mutation of ADAMTS3.

Keywords: ADAMTS3; HKLLS; Hennekam lymphangiectasia-lymphedema syndrome; VEGF.

Publication types

  • Case Reports

MeSH terms

  • ADAMTS Proteins / genetics*
  • Alleles
  • Biopsy
  • Craniofacial Abnormalities / diagnosis*
  • Craniofacial Abnormalities / genetics*
  • Exome Sequencing
  • Genetic Association Studies* / methods
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Infant, Newborn
  • Loss of Function Mutation*
  • Lymphangiectasis, Intestinal / diagnosis*
  • Lymphangiectasis, Intestinal / genetics*
  • Lymphedema / diagnosis*
  • Lymphedema / genetics*
  • Male
  • Phenotype
  • Procollagen N-Endopeptidase / genetics*

Substances

  • ADAMTS Proteins
  • ADAMTS3 protein, human
  • Procollagen N-Endopeptidase

Supplementary concepts

  • Hennekam lymphangiectasia lymphedema syndrome