Recessive Robinow syndrome, allelic to dominant brachydactyly type B, is caused by mutation of ROR2


AFZAL A., RAJAB A., FENSKE C., OLDRIDGE M., ELANKO N., TERNES-PEREIRA E., ...Daha Fazla

NATURE GENETICS, cilt.25, ss.419-422, 2000 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 25 Konu: 4
  • Basım Tarihi: 2000
  • Doi Numarası: 10.1038/78107
  • Dergi Adı: NATURE GENETICS
  • Sayfa Sayıları: ss.419-422

Özet

The autosomal recessive form of Robinow syndrome (RRS; MIM 268310) is a severe skeletal dysplasia with generalized limb bone shortening, segmental defects of the spine, brachydactyly and a dysmorphic facial appearance(1-3). We previously mapped the gene mutated in RRS to chromosome 9q22 (ref. 4), a region that overlaps the locus for autosomal dominant brachydactyly type B (refs 5,6). The recent identification of ROR2, encoding an orphan receptor tyrosine kinase, as the gene mutated in brachydactyly type B (BDB1; ref. 7) and the mesomelic dwarfing in mice homozygous for a lacZ and/or a neo insertion into Ror2 (refs 8.9) made this gene a candidate for RRS. Here we report homozygous missense mutations in both intracellular and extracellular domains of ROR2 in affected individuals from 3 unrelated consanguineous families, and a nonsense mutation that removes the tyrosine kinase domain and all subsequent 3' regions of the gene in 14 patients from 7 families from Oman. The nature of these mutations suggests that RRS is caused by loss of ROR2 activity. The identification of mutations in three distinct domains (containing Frizzled-like, kringle and tyrosine kinase motifs) indicates that these are all essential for ROR2 function.