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Hestand MS, Nowakowska BA, Vergaelen E, et al. A catalog of hemizygous variation in 127 22q11 deletion patients. Hum Genome Var. 2016;3:15065doi: 10.1038/hgv.2015.65.
Hestand, M. S., Nowakowska, B. A., Vergaelen, E., Van Houdt, J., Dehaspe, L., Suhl, J. A., Del-Favero, J., Mortier, G., Zackai, E., Swillen, A., Devriendt, K., Gur, R. E., McDonald-McGinn, D. M., Warren, S. T., Emanuel, B. S., & Vermeesch, J. R. (2016). A catalog of hemizygous variation in 127 22q11 deletion patients. Human genome variation, 315065. https://doi.org/10.1038/hgv.2015.65
Hestand, Matthew S, et al. "A catalog of hemizygous variation in 127 22q11 deletion patients." Human genome variation vol. 3 (2016): 15065. doi: https://doi.org/10.1038/hgv.2015.65
Hestand MS, Nowakowska BA, Vergaelen E, Van Houdt J, Dehaspe L, Suhl JA, Del-Favero J, Mortier G, Zackai E, Swillen A, Devriendt K, Gur RE, McDonald-McGinn DM, Warren ST, Emanuel BS, Vermeesch JR. A catalog of hemizygous variation in 127 22q11 deletion patients. Hum Genome Var. 2016 Jan 14;3:15065. doi: 10.1038/hgv.2015.65. eCollection 2016. PMID: 27274857; PMCID: PMC4892188.
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Hum Genome Var. 2016 Jan 14;3:15065. doi: 10.1038/hgv.2015.65. eCollection 2016.

A catalog of hemizygous variation in 127 22q11 deletion patients.

Human genome variation

Matthew S Hestand, Beata A Nowakowska, Elfi Vergaelen, Jeroen Van Houdt, Luc Dehaspe, Joshua A Suhl, Jurgen Del-Favero, Geert Mortier, Elaine Zackai, Ann Swillen, Koenraad Devriendt, Raquel E Gur, Donna M McDonald-McGinn, Stephen T Warren, Beverly S Emanuel, Joris R Vermeesch

Affiliations

  1. Department of Human Genetics, KU Leuven , Leuven, Belgium.
  2. Department of Human Genetics, KU Leuven, Leuven, Belgium; Institute of Mother and Child, Warsaw, Poland.
  3. Department of Human Genetics, KU Leuven, Leuven, Belgium; Genomics Core, UZ Leuven, Leuven, Belgium.
  4. Genomics Core, UZ Leuven , Leuven, Belgium.
  5. Department of Human Genetics, Emory University School of Medicine , Atlanta, GA, USA.
  6. VIB Departement Moleculaire Genetica, University of Antwerp , Antwerp, Belgium.
  7. Department of Medical Genetics, Antwerp University Hospital , Edegem, Belgium.
  8. Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  9. Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, USA.

PMID: 27274857 PMCID: PMC4892188 DOI: 10.1038/hgv.2015.65

Abstract

The 22q11.2 deletion syndrome is the most common microdeletion disorder, with wide phenotypic variability. To investigate variation within the non-deleted allele we performed targeted resequencing of the 22q11.2 region for 127 patients, identifying multiple deletion sizes, including two deletions with atypical breakpoints. We cataloged ~12,000 hemizygous variant positions, of which 84% were previously annotated. Within the coding regions 95 non-synonymous variants, three stop gains, and two frameshift insertions were identified, some of which we speculate could contribute to atypical phenotypes. We also catalog tolerability of 22q11 gene mutations based on related autosomal recessive disorders in man, embryonic lethality in mice, cross-species conservation and observations that some genes harbor more or less variants than expected. This extensive catalog of hemizygous variants will serve as a blueprint for future experiments to correlate 22q11DS variation with phenotype.

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