Exome sequencing identifies a recessive PIGN splice site mutation as a cause of syndromic congenital diaphragmatic hernia.
Using exome sequencing we identify a homozygous splice site mutation in the PIGN gene in a foetus with multiple congenital anomalies including bilateral diaphragmatic hernia, cardiovascular anomalies, segmental renal dysplasia, facial dysmorphism, cleft palate, and oligodactyly. This finding expands the phenotypic spectrum associated with homozygous loss of function mutations in PIGN, and adds further support for defective GPI anchor biosynthesis as a cause of developmental abnormalities. We demonstrate that exome sequencing is a valuable approach for the identification of a genetic cause in sporadic cases of multiple congenital anomalies (MCA) due to inherited mutations.
Centre for Human Genetics, KU Leuven, University Hospital Leuven, Belgium.
P D
PD
Brady
Translational Cell & Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, University Hospital Leuven, Belgium.
Philippe
P
Moerman
Department of Development and Regeneration, Unit Pregnancy, Foetus and Newborn, KU Leuven, University Hospital Leuven, Belgium; Department Obstetrics and Gynaecology, University Hospital Leuven, Belgium.
Luc
L
De Catte
Department of Development and Regeneration, Unit Pregnancy, Foetus and Newborn, KU Leuven, University Hospital Leuven, Belgium; Department Obstetrics and Gynaecology, University Hospital Leuven, Belgium.
J
J
Deprest
Centre for Human Genetics, KU Leuven, University Hospital Leuven, Belgium.
K
K
Devriendt
Centre for Human Genetics, KU Leuven, University Hospital Leuven, Belgium. Electronic address: Joris.vermeesch@uz.kuleuven.ac.be.
J R
JR
Vermeesch
D037881:Aborted Fetus / Q000473:pathology; D002874:Chromosome Mapping; D003241:Consanguinity; D059472:Exome; D005808:Genes, Recessive; D005838:Genotype; D065630:Hernias, Diaphragmatic, Congenital / Q000175:diagnosis / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D010375:Pedigree; D010770:Phosphotransferases / Q000235:genetics*; D022821:RNA Splice Sites; D013577:Syndrome
D022821:RNA Splice Sites; C561296:PIGN protein, human; D010770:Phosphotransferases
CDH; Congenital Diaphragmatic Hernia; Exome sequencing; GPI anchor; PIGN