PCDH19-related epileptic encephalopathy in a male mosaic for a truncating variant.

Document Type

Article

Publication Date

6-2016

Identifier

DOI: 10.1002/ajmg.a.37617

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.

Journal Title

American journal of medical genetics. Part A

Volume

170

Issue

6

First Page

1585

Last Page

1589

MeSH Keywords

Cadherins; Child; DNA Mutational Analysis; Electroencephalography; Epilepsy; Exome; Genetic Association Studies; High-Throughput Nucleotide Sequencing; Humans; Male; Mosaicism; Mutation; Neuropsychological Tests; Phenotype

Keywords

PCDH19; behavioral disorders; developmental disorders; dysmorphic features; epileptic encephalopathy; somatic mosaicism

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