The gene for branchio-oculo-facial syndrome does not colocalise to the EYA1-4 genes

Editor—The branchio-oculo-facial syndrome (BOFS) is characterised by a branchial cleft sinus or linear skin lesion behind the ear, lacrimal duct obstruction, colobomata of the iris/retina, hypertrophy of the lateral pillars of the philtrum (“pseudocleft”), an asymmetrical nose with a broad tip, and auricular and lip pits. Premature greying of the hair is also observed.1 Inheritance is autosomal dominant (OMIM 113620).2 Several anomalies common to both BOF and BOR (branchio-oto-renal) syndromes have been reported.3 McCool and Weaver4 reported three cases with BOF and unilateral renal agenesis. This anomaly is not frequent in BOFS but is characteristic for patients with BOR, and hence a contiguous gene syndrome or the presence of different mutations within a single gene have been suggested.4 Recently, the BOR gene was identified by positional cloning on chromosome 8q13.3 and mapped between markers D8S1060 and D8S1807.5 The gene was named “eyes absent-like 1” ( EYA1 ), the human homologue of the Drosophila eyes absent gene. It has been postulated that the EYA1 gene and two other EYA related genes ( EYA2 on chromosome 20q13.1 and EYA3 on 1p36) play a role in development.5 Based on the largest published family with BOFS6 and in order to find a candidate gene for BOFS, we studied four flanking markers in the BOR chromosome region ( EYA1 gene)7 as well as six markers flanking the EYA2 gene,8 four markers at the EYA3 gene,9 and four markers close to the EYA4 gene, which has recently been mapped to 6q23.10 The family studied here was described in detail by Lin et al …