Identification of a novel Bardet-Biedl syndrome protein, BBS7, that shares structural features with BBS1 and BBS2

Am J Hum Genet. 2003 Mar;72(3):650-8. doi: 10.1086/368204. Epub 2003 Feb 3.


Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder, the primary features of which include obesity, retinal dystrophy, polydactyly, hypogenitalism, learning difficulties, and renal malformations. Conventional linkage and positional cloning have led to the mapping of six BBS loci in the human genome, four of which (BBS1, BBS2, BBS4, and BBS6) have been cloned. Despite these advances, the protein sequences of the known BBS genes have provided little or no insight into their function. To delineate functionally important regions in BBS2, we performed phylogenetic and genomic studies in which we used the human and zebrafish BBS2 peptide sequences to search dbEST and the translation of the draft human genome. We identified two novel genes that we initially named "BBS2L1" and "BBS2L2" and that exhibit modest similarity with two discrete, overlapping regions of BBS2. In the present study, we demonstrate that BBS2L1 mutations cause BBS, thereby defining a novel locus for this syndrome, BBS7, whereas BBS2L2 has been shown independently to be BBS1. The motif-based identification of a novel BBS locus has enabled us to define a potential functional domain that is present in three of the five known BBS proteins and, therefore, is likely to be important in the pathogenesis of this complex syndrome.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Alternative Splicing
  • Amino Acid Sequence
  • Bardet-Biedl Syndrome / genetics*
  • Chromosome Mapping
  • Cytoskeletal Proteins
  • DNA / blood
  • DNA / genetics
  • DNA / isolation & purification
  • Exons
  • Female
  • Fetus
  • Genes, Recessive
  • Genetic Variation
  • Humans
  • Male
  • Microtubule-Associated Proteins
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Protein Isoforms / genetics
  • Proteins / chemistry
  • Proteins / genetics*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcription, Genetic


  • Adaptor Proteins, Signal Transducing
  • Bbs1 protein, human
  • Bbs2 protein, human
  • Bbs7 protein, human
  • Cytoskeletal Proteins
  • Microtubule-Associated Proteins
  • Protein Isoforms
  • Proteins
  • DNA

Associated data

  • GENBANK/AF521643
  • GENBANK/AF521644
  • GENBANK/AF521645
  • OMIM/209900