How to Cite this Article: Wannasilp N, Solomon BD, Warren-Mora N, Clegg NJ, Delgado MR, Lacbawan F, Hu P, Winder TL, Roessler E, Muenke M. 2011. Holoprosencephaly in a family segregating novel variants in ZIC2 and GLI2. Am J Med Genet Part A 155:860–864.
Holoprosencephaly in a family segregating novel variants in ZIC2 and GLI2†
Article first published online: 17 MAR 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 155, Issue 4, pages 860–864, April 2011
How to Cite
Wannasilp, N., Solomon, B. D., Warren-Mora, N., Clegg, N. J., Delgado, M. R., Lacbawan, F., Hu, P., Winder, T. L., Roessler, E. and Muenke, M. (2011), Holoprosencephaly in a family segregating novel variants in ZIC2 and GLI2. Am. J. Med. Genet., 155: 860–864. doi: 10.1002/ajmg.a.33903
- Issue published online: 24 MAR 2011
- Article first published online: 17 MAR 2011
- Manuscript Accepted: 23 DEC 2010
- Manuscript Received: 29 AUG 2010
- Division of Intramural Research
- National Human Genome Research Institute
- National Institutes of Health
- Department of Health and Human Services, United States of America
- Don and Linda Carter Foundation
- Crowley-Carter Foundation.
Additional supporting information may be found in the online version of this article.
|AJMA_33903_sm_Suppl-Fig-1.tif||369K||Fig. 1: A multiple alignment (NCBI COBALT) comparison of related sequences obtained by a protein BLAST search (http://blast.ncbi.nlm.nih.gov/Blast.cgi) was generated of the N-terminal Regulatory motif (NR in red, see ) consisting of the Degron N motif and SUFU binding site (in green) as arranged by GLI 1, 2 or 3 family types. Aminoacid differences from the top reference line are indicated by the symbol "X". Interestingly, all detected mis-sense changes (highlighted by an orange arrow) 1) c.677G>A (p.Arg226His) 2) the putative SNP c.686G>T (p.Arg229Leu) and 3) the c.691 C>T (p.Arg231Trp) occur at residues conserved in all examples of vertebrate Gli2 and Gli3 protein sequences. Within the GLI1 family the orange marked ("X") residues are the similarly charges aminoacid Lys. Taken together, the similar conservation properties of all three examples does not allow for a clear distinction between likely mutations (p.Arg226His) and (p.Arg231Trp) and rare population variants seen in normal individuals (p.Arg229Leu).|
|AJMA_33903_sm_Suppl-Table-I.doc||50K||Table I: Summary of the variants identified in GLI2 [RefSeq ID: NM_005270] exon 6 (c.644_845) normal control genotypes. Neither the c.677G>A (the variant in the family described here) nor the c.691 C>T (a variant found in an unrelated proband with HPE) changes were found in 1096 human control chromosomes by direct sequencing. The c.677G>A variant was also not found in 928 human control chromosomes by TaqMan assay.|
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