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J Med Genet 37:623-627 doi:10.1136/jmg.37.8.623
  • Letters to the editor

Importance of clinical evaluation and molecular testing in the branchio-oto-renal (BOR) syndrome and overlapping phenotypes

  1. SARAH RICKARD*,
  2. MAUREEN BOXER*,
  3. RICHARD TROMPETER,
  4. MARIA BITNER-GLINDZICZ
  1. * The North Thames (East) Regional Clinical Molecular Genetics Laboratory, Level 5, Camelia Botnar Laboratories, Great Ormond Street, London WC1N 3JH, UK
  2. Nephrourology Unit, Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, UK
  3. Units of Clinical and Molecular Genetics, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
  1. Dr Bitner-Glindzicz,mbitnerg{at}hgmp.mrc.ac.uk

    Editor—The branchio-oto-renal (BOR) syndrome was first reported in the last century by Heusinger, but not clinically defined until 1976 by Melnick et al.1 The major clinical features associated with the BOR syndrome are hearing loss, branchial defects, ear pits, and renal anomalies.1 Hearing loss can be conductive, sensorineural, or mixed, ranging from mild to profound deafness.2 Renal abnormalities are also variable, including renal aplasia, hypoplasia, and dysplasia, as well as anomalies of the collecting system.3 Branchial defects including fistulas or cysts and ear pits are often observed, and minor features such as external ear abnormalities, ear tags, and lacrimal duct aplasia are sometimes present. The BOR syndrome is inherited in an autosomal dominant manner and penetrance is high, although expressivity can be extremely variable.3-5

    The BOR syndrome gene was localised to 8q following the description of a person with an inherited rearrangement, dir ins(8)(q24.11:q13.3:q21.13) presenting with features of both the branchio-oto (BO) syndrome and trichorhinophalangeal syndrome.6 Linkage analysis confirmed that the BOR syndrome mapped to 8q13.3.7 8 Further fine mapping defined the BOR region to be a 450-650 kb interval.9-12In 1997, the gene was cloned by sequencing P1/PAC clones from a contig spanning the region, yielding sequences homologous to theDrosophila developmental geneeyes absent (eya).Point mutations and deletions were subsequently detected in the human homologue, EYA1, in families with the BOR syndrome.13 14

    EYA1 consists of 16 coding exons and encodes a 559 amino acid protein. There are two additionalEYA1 isoforms and all show significant homology to the Drosophila eya gene, as well as to the murine homologue, constituting a novel gene family.14 15 The Drosophila eya gene is essential in the formation of the fly compound eye and the pathway has …