Citations 2
Mouse model implicates GNB3 duplication in a childhood obesity syndrome
Goldlust, Ian S. , Hermetz, Karen , Catalano, Lisa M., Barfield, Richard , Cozad, Rebecca, Wynn, Grace M., Ozdemir, Alev Cagla, Conneely, Karen N. , Mullé, Jennifer G. , Dharamrup, Shikha, Hegde, Madhuri , Kim, Katherine H. , Angle, Brad, Colley, Alison, Thorland, Erik C., Ellison, Jay W., Ballif, Blake C., Shaffer, Lisa G. , Demmer, Laurie , Group, Unique Rare Chromosome Disorder Support, Rudd, M. Katharine , Searle, Beverly A., Wynn, Sarah , Webb, Amy , Rosenfeld, Jill A. , Group, Unique Rare Chromosome Disorder Support
Proceedings of the National Academy of Sciences | August 26, 2013 | Volume: 110 | Issue: 37 | Pages: 14990-14994
Significance We describe a genomic disorder that causes obesity, intellectual disability, and seizures. Children with this syndrome carry an unbalanced chromosome translocation that results in the duplication of over 100 genes, including G protein β3 ( GNB3 ). Although GNB3 polymorphisms have been associated with obesity, hypertension, and diabetes, the mechanism of GNB3 pathogenesis is unknown. We created a transgenic mouse model that carries a duplication of GNB3 , weighs significantly more than wild-type mice, and has excess abdominal fat. GNB3 is highly expressed in the brain and may be important for signaling related to satiety and/or metabolism.
Deletions in 16q24.2 are associated with autism spectrum disorder, intellectual disability and congenital renal malformation
Handrigan, Gregory R., Lionel, Anath C. , Pinsk, Maury , Vaags, Andrea K., Marshall, Christian R. , Dyack, Sarah , Fernandez, Bridget A. , Stegman, Joseph C., Shaffer, Lisa G. , Goodenberger, McKinsey L. , Hodge, Jennelle C. , Cain, Jason E. , Babul‐Hirji, Riyana, Stavropoulos, Dimitri J. , Yiu, Verna, Scherer, Stephen W. , Rosenblum, Norman D. , Chitayat, David A. , Escobar, Luis Fernando , Rosenfeld, Jill A. , Scherer, Stephen W , Goodenberger, McKinsey
Journal of Medical Genetics | January 18, 2013 | Volume: 50 | Issue: 3 | Pages: 163-173
Background The contribution of copy-number variation (CNV) to disease has been highlighted with the widespread adoption of array-based comparative genomic hybridisation (aCGH) and microarray technology. Contiguous gene deletions involving ANKRD11 in 16q24.3 are associated with autism spectrum disorder (ASD) and intellectual disability (ID), while 16q24.1 deletions affecting FOXF1 are associated with congenital renal malformations, alveolar capillary dysplasia, and various other abnormalities. The disease associations of deletions in the intervening region, 16q24.2, have only been defined to a limited extent. Aim To determine whether deletions affecting 16q24.2 are correlated with congenital anomalies. Methods 35 individuals, each having a deletion in 16q24.2, were characterised clinically and by aCGH and/or SNP-genotyping microarray. Results Several of the 35 16q24.2 deletions identified here closely abut or overlap the coding regions of FOXF1 and ANKRD11, two genes that have been previously associated with the disease. 25 patients were reported to have ASD/ID, and three were found to have bilateral hydronephrosis. 14 of the deletions associated with ASD/ID overlap the coding regions of FBXO31 and MAP1LC3B. These same genes and two others, C16orf95 and ZCCHC14, are also included in the area of minimal overlap of the three deletions associated with hydronephrosis. Conclusions Our data highlight 16q24.2 as a region of interest for ASD, ID and congenital renal malformations. These conditions are associated, albeit without complete penetrance, with deletions affecting C16orf95, ZCCHC14, MAP1LC3B and FBXO31. The function of each gene in development and disease warrants further investigation.