Editor—The Townes-Brocks syndrome (TBS, MIM 107480) is an autosomal dominantly inherited association of imperforate anus, supernumerary/triphalangeal thumbs, and dysplastic ears. In addition to this, sensorineural or conductive hearing loss, renal malformations, cardiac defects, and mental retardation maybe present in affected subjects. TBS is caused by mutations of the putative zinc finger transcription factor geneSALL1.2 SALL1 has four double zinc finger domains which are evenly distributed over the protein.3 The majority of SALL1mutations identified to date in TBS patients are located 5′ to the first double zinc finger encoding region.4 5 Most mutations (nonsense mutations, small insertions/deletions, and one larger deletion) have been predicted to result in prematurely truncated proteins lacking all double zinc finger domains presumed to be essential for SALL1 gene function or to result in unstable transcripts, thus causing TBS via haploinsufficiency.4 5

TBS is known to overlap phenotypically with other conditions like Goldenhar syndrome, VACTERL association, or oculo-auriculo-vertrebral spectrum.1 However, a SALL1mutation has so far only been reported in one patient with a clinical picture attributable both to Goldenhar syndrome and TBS.6This patient, as well as the TBS patients in whom mutations were detected, showed at least two out of three major criteria for TBS, that is, malformations of the thumbs, ears, or anus.4 5Therefore, the phenotypic spectrum associated withSALL1 mutations seemed to be quite characteristic.

Here we report the first family in which aSALL1 mutation is associated with a phenotype which is different from TBS. …