How to Cite this Article: Campbell IM, Kolodziejska KE, Quach M, Wolf VL, Cheung SW, Lalani SR, Ramocki MB, Stankiewicz P. 2011. TGFBR2 deletion in a 20-month-old female with developmental delay and microcephaly. Am J Med Genet Part A 155:1442–1447.
TGFBR2 deletion in a 20-month-old female with developmental delay and microcephaly†
Article first published online: 12 MAY 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 155, Issue 6, pages 1442–1447, June 2011
How to Cite
Campbell, I. M., Kolodziejska, K. E., Quach, M. M., Wolf, V. L., Cheung, S. W., Lalani, S. R., Ramocki, M. B. and Stankiewicz, P. (2011), TGFBR2 deletion in a 20-month-old female with developmental delay and microcephaly. Am. J. Med. Genet., 155: 1442–1447. doi: 10.1002/ajmg.a.34015
- Issue published online: 20 MAY 2011
- Article first published online: 12 MAY 2011
- Manuscript Accepted: 7 MAR 2011
- Manuscript Received: 12 JAN 2011
- Polish Ministry of Science and Higher Education. Grant Number: R13-0005-04/2008
- NIH/NINDS. Grant Number: 5K08NS062711-03
- somatic mosaicism;
- TGF-β signaling;
- Loeys–Dietz syndrome
To date, over 70 mutations in the TGFBR2 gene have been reported in patients with Loeys–Dietz syndrome (LDS), Marfan syndrome type 2 (MFS2), or other hereditary thoracic aortic aneurysms and dissections. Whereas almost all of mutations analyzed thus far are predicted to disrupt the constitutively active C-terminal serine/threonine kinase domain of TGFBR2, mounting evidence suggests that the molecular mechanism underlying these diseases is more complex than simple haploinsufficiency. Using exon-targeted oligonucleotide array comparative genomic hybridization, we identified an ∼896 kb deletion of TGFBR2 in a 20-month-old female with microcephaly and global developmental delay, but no stigmata of LDS. FISH analysis showed no evidence of this deletion in the parental peripheral blood samples; however, somatic mosaicism was detected using PCR in the paternal DNA from peripheral blood lymphocytes and lymphoblasts. Our data suggest that TGFBR2 haploinsufficiency may cause a phenotype, which is distinct from LDS. Moreover, we propose that somatic mosaicism below the detection threshold of FISH analysis in asymptomatic parents of children with genomic disorders may be more common than previously recognized. © 2011 Wiley-Liss, Inc.