Year: 2019
Type: article
Study design: Case Report
Abstract: Hennekam lymphangiectasia-lymphedema syndrome is an autosomal recessive disorder characterized by congenital lymphedema, intestinal lymphangiectasia, facial dysmorphism, and variable intellectual disability. Known disease genes include CCBE1, FAT4, and ADAMTS3. In a patient with clinically diagnosed Hennekam syndrome but without mutations or copy-number changes in the three known disease genes, we identified a homozygous single-exon deletion affecting FBXL7. Specifically, exon 3, which encodes the F-box domain and several leucine-rich repeats of FBXL7, is eliminated. Our analyses of databases representing >100,000 control individuals failed to identify biallelic loss-of-function variants in FBXL7. Published studies in Drosophila indicate Fbxl7 interacts with Fat, of which human FAT4 is an ortholog, and mutation of either gene yields similar morphological consequences. These data suggest that FBXL7 may be the fourth gene for Hennekam syndrome, acting via a shared pathway with FAT4.
DOI: 10.1002/ajmg.a.61392
Institutions: Broad Institute, Boston Children's Hospital, Harvard University, Massachusetts General Hospital, Stanley Center for Psychiatric Research, Massachusetts Institute of Technology, The University of Queensland, Institute for Molecular Bioscience, Baylor Genetics, Manton Center for Orphan Disease Research
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: National Science Foundation, National Institutes of Health, Manton Center for Orphan Disease Research, Boston Children's Hospital, National Health and Medical Research Council, National Institute of Mental Health, National Institute of General Medical Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
OpenAlex ID: W2981664313