Please cite this article as follows: Ruf N, Uhlenberg B. 2009. Analysis of Human Alternative First Exons and Copy Number Variation of the GJA12 Gene in Patients With Pelizaeus–Merzbacher-Like Disease. Am J Med Genet Part B 150B:226–232.
Analysis of human alternative first exons and copy number variation of the GJA12 gene in patients with Pelizaeus–Merzbacher-like disease†
Article first published online: 2 JUN 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 150B, Issue 2, pages 226–232, 5 March 2009
How to Cite
Ruf, N. and Uhlenberg, B. (2009), Analysis of human alternative first exons and copy number variation of the GJA12 gene in patients with Pelizaeus–Merzbacher-like disease. Am. J. Med. Genet., 150B: 226–232. doi: 10.1002/ajmg.b.30792
- Issue published online: 19 FEB 2009
- Article first published online: 2 JUN 2008
- Manuscript Accepted: 28 APR 2008
- Manuscript Received: 8 FEB 2008
- Deutsche Forschungsgemeinschaft. Grant Number: SFB 665
- gap junction proteins;
- candidate genes
Pelizaeus–Merzbacher-like disease (PMLD) is a heterogeneous disease with primary hypomyelination of the central nervous system. Only the minority of patients have mutations in the coding region of the GJA12 gene encoding gap junction protein alpha 12, a subunit of intercellular channels highly expressed by oligodendrocytes, the myelin forming cells of the central nervous system. No other gene has been found so far to be mutated in PMLD besides GJA12. We therefore extended the mutational screening in the GJA12 gene, searched for alternative first exons—as described in mice—determined the human 5′-end of the gene, screened therein for mutations and analyzed for copy number variations of the GJA12 gene in 14 patients with PMLD. Unlike in mice we did not find alternative first exons but detected a unique 79 bp first exon in human adolescent brain and spinal cord. No mutation in this non-coding region was found in our cohort. Copy number variation of the GJA12 gene was assessed by real-time PCR TaqMan® gene expression technology, but neither patient showed an aberrant copy number. These data confirm that GJA12 alterations are a rare cause of PMLD—even after extending the screening for copy number variation and for mutations in the non-coding region of GJA12. Full genome scans in informative families and further screenings of candidate genes are feasible approaches to elucidate the genetic background of the majority of patients with PMLD. © 2008 Wiley-Liss, Inc.