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<p>Abstract</p> <p>Background</p> <p>A disruption of sorting nexin 3 (<it>SNX3</it>) on 6q21 was previously reported in a patient with MMEP (microcephaly, microphthalmia, ectrodactyly, and prognathism) and t(6;13)(q21;q12) but no <it>SNX3 </it>mutations were identified in another sporadic case of MMEP, suggesting involvement of another gene. In this work, <it>SNX3 </it>was sequenced in three patients not previously studied for this gene. In addition, we test the hypothesis that mutations in the neighbouring gene <it>NR2E1 </it>may underlie MMEP and related phenotypes.</p> <p>Methods</p> <p>Mutation screening was performed in five patients: the t(6;13)(q21;q12) MMEP patient, three additional patients with possible MMEP or a related phenotype, and one patient with oligodactyly, ulnar aplasia, and a t(6;7)(q21;q31.2) translocation. We used sequencing to exclude <it>SNX3 </it>coding mutations in three patients not previously studied for this gene. To test the hypothesis that mutations in <it>NR2E1 </it>may contribute to MMEP or related phenotypes, we sequenced the entire coding region, complete 5' and 3' untranslated regions, consensus splice-sites, and evolutionarily conserved regions including core and proximal promoter in all five patients. Two-hundred and fifty control subjects were genotyped for any candidate mutation.</p> <p>Results</p> <p>We did not detect any synonymous nor nonsynonymous coding mutations of <it>NR2E1 </it>or <it>SNX3</it>. In one patient with possible MMEP, we identified a candidate regulatory mutation that has been reported previously in a patient with microcephaly but was not found in 250 control subjects examined here.</p> <p>Conclusion</p> <p>Our results do not support involvement of coding mutations in <it>NR2E1 </it>or <it>SNX3 </it>in MMEP or related phenotypes; however, we cannot exclude the possibility that regulatory <it>NR2E1 </it>or <it>SNX3 </it>mutations or deletions at this locus may underlie abnormal human cortical development in some patients.</p>