Email updates

Keep up to date with the latest news and content from BMC Medical Genetics and BioMed Central.

Open Access Research article

Absence of mutations in NR2E1 and SNX3 in five patients with MMEP (microcephaly, microphthalmia, ectrodactyly, and prognathism) and related phenotypes

Ravinesh A Kumar1, David B Everman2, Chad T Morgan2, Anne Slavotinek3, Charles E Schwartz2 and Elizabeth M Simpson1*

Author Affiliations

1 Centre for Molecular Medicine and Therapeutics, Child & Family Research Institute, Department of Medical Genetics, University of British Columbia, 950 West 28th Ave, Vancouver, V5Z 4H4, Canada

2 Center for Molecular Studies, J.C. Self Research Institute, Greenwood Genetic Center. One Gregor Mendel Circle, Greenwood, South Carolina, 29646, USA

3 Department of Pediatrics, Division of Medical Genetics, University of California, Box 0748, 533 Parnassus St., San Francisco, California, 94143-0748, USA

For all author emails, please log on.

BMC Medical Genetics 2007, 8:48  doi:10.1186/1471-2350-8-48

Published: 26 July 2007

Abstract

Background

A disruption of sorting nexin 3 (SNX3) on 6q21 was previously reported in a patient with MMEP (microcephaly, microphthalmia, ectrodactyly, and prognathism) and t(6;13)(q21;q12) but no SNX3 mutations were identified in another sporadic case of MMEP, suggesting involvement of another gene. In this work, SNX3 was sequenced in three patients not previously studied for this gene. In addition, we test the hypothesis that mutations in the neighbouring gene NR2E1 may underlie MMEP and related phenotypes.

Methods

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 SNX3 coding mutations in three patients not previously studied for this gene. To test the hypothesis that mutations in NR2E1 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.

Results

We did not detect any synonymous nor nonsynonymous coding mutations of NR2E1 or SNX3. 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.

Conclusion

Our results do not support involvement of coding mutations in NR2E1 or SNX3 in MMEP or related phenotypes; however, we cannot exclude the possibility that regulatory NR2E1 or SNX3 mutations or deletions at this locus may underlie abnormal human cortical development in some patients.