title: PCDH19-related epileptic encephalopathy in a male mosaic for a truncating variant.
abstract: Variants in the X-linked gene PCDH19 are associated with early infantile epileptic encephalopathy-9. This unusual condition spares hemizygous males except for psychiatric and behavioral abnormalities, and for this reason is also known as female limited epilepsy. Some cases are due to de novo PCDH19 variants, but may also be paternally inherited. Our patient is a 6-year-old male with epileptic encephalopathy. Exome sequencing revealed apparent heterozygosity in PCDH19 for a novel nonsense variant, c.605C>A (p.Ser202*), inconsistent with expectations for a male. Testing of other tissues revealed a mixture of mutant and normal alleles. These results are consistent with somatic mosaicism for p.Ser202*. This is the second male with somatic mosaicism for PCDH19 deficiency, providing further support for cellular interference as the pathogenic mechanism for this condition, which leads to this unusual mode of inheritance in which females are more severely affected than males. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri.|Department of Pathology and Laboratory Medicine, Children's Mercy Hospitals, Kansas City, Missouri.|University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Thiffault
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri.|University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
authors.forename: Emily
authors.initials: E
authors.lastname: Farrow
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri.|Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Laurie
authors.initials: L
authors.lastname: Smith
authors.affiliation: University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.|Individualized Pediatric Therapeutic Medicine Clinic, Children's Mercy Hospital, Kansas City, Missouri.|Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lowry
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri.
authors.forename: Lee
authors.initials: L
authors.lastname: Zellmer
authors.affiliation: Individualized Pediatric Therapeutic Medicine Clinic, Children's Mercy Hospital, Kansas City, Missouri.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Black
authors.affiliation: Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdelmoity
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri.
authors.forename: Neil
authors.initials: N
authors.lastname: Miller
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri.|University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.|Individualized Pediatric Therapeutic Medicine Clinic, Children's Mercy Hospital, Kansas City, Missouri.|Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri.
authors.forename: Sarah
authors.initials: S
authors.lastname: Soden
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri.|Department of Pathology and Laboratory Medicine, Children's Mercy Hospitals, Kansas City, Missouri.|University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
authors.forename: Carol
authors.initials: C
authors.lastname: Saunders
mesh_terms: D015820:Cadherins / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004827:Epilepsy / Q000175:diagnosis* / Q000235:genetics*; D059472:Exome; D056726:Genetic Association Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009030:Mosaicism; D009154:Mutation; D009483:Neuropsychological Tests; D010641:Phenotype; D000091363:Protocadherins
chemical_list: D015820:Cadherins; C438605:PCDH19 protein, human; D000091363:Protocadherins
keywords: PCDH19; behavioral disorders; developmental disorders; dysmorphic features; epileptic encephalopathy; somatic mosaicism