Identification of critical regions and candidate genes for Cardiovascular malformations and cardiomyopathy associated with deletions of chromosome 1p36

Hitisha P. Zaveri, Tyler F. Beck, Andrés Hernández-García, Katharine E. Shelly, Tara Montgomery, Arie Van Haeringen, Britt Marie Anderlid, Chirag Patel, Himanshu Goel, Gunnar Houge, Bernice E. Morrow, Sau Wai Cheung, Seema R. Lalani, Daryl A. Scott

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24 Scopus citations

Abstract

Cardiovascular malformations and cardiomyopathy are among the most common phenotypes caused by deletions of chromosome 1p36 which affect approximately 1 in 5000 newborns. Although these cardiac-related abnormalities are a significant source of morbidity and mortality associated with 1p36 deletions, most of the individual genes that contribute to these conditions have yet to be identified. In this paper, we use a combination of clinical and molecular cytogenetic data to define five critical regions for cardiovascular malformations and two critical regions for cardiomyopathy on chromosome 1p36. Positional candidate genes which may contribute to the development of cardiovascular malformations associated with 1p36 deletions include DVL1, SKI, RERE, PDPN, SPEN, CLCNKA, ECE1, HSPG2, LUZP1, and WASF2. Similarly, haploinsufficiency of PRDM16-a gene which was recently shown to be sufficient to cause the left ventricular noncompaction-SKI, PRKCZ, RERE, UBE4B and MASP2 may contribute to the development of cardiomyopathy. When treating individuals with 1p36 deletions, or providing prognostic information to their families, physicians should take into account that 1p36 deletions which overlie these cardiac critical regions may portend to cardiovascular complications. Since several of these cardiac critical regions contain more than one positional candidate gene- and large terminal and interstitial 1p36 deletions often overlap more than one cardiac critical region-it is likely that haploinsufficiency of two or more genes contributes to the cardiac phenotypes associated with many 1p36 deletions. Copyright:

Original languageEnglish (US)
Article numbere85600
JournalPloS one
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 15 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Zaveri, H. P., Beck, T. F., Hernández-García, A., Shelly, K. E., Montgomery, T., Van Haeringen, A., ... Scott, D. A. (2014). Identification of critical regions and candidate genes for Cardiovascular malformations and cardiomyopathy associated with deletions of chromosome 1p36. PloS one, 9(1), [e85600]. https://doi.org/10.1371/journal.pone.0085600