A catalog of hemizygous variation in 127 22q11 deletion patients.
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.
Department of Human Genetics, KU Leuven , Leuven, Belgium.
Matthew S
MS
Hestand
Department of Human Genetics, KU Leuven, Leuven, Belgium; Institute of Mother and Child, Warsaw, Poland.
Beata A
BA
Nowakowska
Department of Human Genetics, KU Leuven , Leuven, Belgium.
Elfi
E
Vergaelen
Department of Human Genetics, KU Leuven, Leuven, Belgium; Genomics Core, UZ Leuven, Leuven, Belgium.
Jeroen
J
Van Houdt
Genomics Core, UZ Leuven , Leuven, Belgium.
Luc
L
Dehaspe
Department of Human Genetics, Emory University School of Medicine , Atlanta, GA, USA.
Joshua A
JA
Suhl
VIB Departement Moleculaire Genetica, University of Antwerp , Antwerp, Belgium.
Jurgen
J
Del-Favero
Department of Medical Genetics, Antwerp University Hospital , Edegem, Belgium.
Geert
G
Mortier
Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Elaine
E
Zackai
Department of Human Genetics, KU Leuven , Leuven, Belgium.
Ann
A
Swillen
Department of Human Genetics, KU Leuven , Leuven, Belgium.
Koenraad
K
Devriendt
Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, USA.
Raquel E
RE
Gur
Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Donna M
DM
McDonald-McGinn
Department of Human Genetics, Emory University School of Medicine , Atlanta, GA, USA.
Stephen T
ST
Warren
Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Beverly S
BS
Emanuel
Department of Human Genetics, KU Leuven , Leuven, Belgium.
Joris R
JR
Vermeesch