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Title: A systematic review and meta-analysis of 271 PCDH19-variant individuals identifies psychiatric comorbidities, and association of seizure onset and disease severity.
Austin Authors: Kolc, Kristy L;Sadleir, Lynette G;Scheffer, Ingrid E ;Ivancevic, Atma;Roberts, Rachel;Pham, Duyen H;Gecz, Jozef
Affiliation: Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia
Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia
School of Psychology, The University of Adelaide, Adelaide, SA, Australia
Healthy Mothers and Babies, South Australian Health and Medical Research Institute, Adelaide, SA, Australia
Department of Paediatrics, Royal Children's Hospital, The University of Melbourne, Melbourne, Victoria, Australia
The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia
Issue Date: 2019 2018-06-11
Publication information: Molecular psychiatry 2019; 24(2): 241-251
Abstract: Epilepsy and Mental Retardation Limited to Females (EFMR) is an infantile onset disorder characterized by clusters of seizures. EFMR is due to mutations in the X-chromosome gene PCDH19, and is underpinned by cellular mosaicism due to X-chromosome inactivation in females or somatic mutation in males. This review characterizes the neuropsychiatric profile of this disorder and examines the association of clinical and molecular factors with neuropsychiatric outcomes. Data were extracted from 38 peer-reviewed original articles including 271 individual cases. We found that seizure onset ≤12 months was significantly associated (p = 4.127 × 10-7) with more severe intellectual disability, compared with onset >12 months. We identified two recurrent variants p.Asn340Ser and p.Tyr366Leufs*10 occurring in 25 (20 unrelated) and 30 (11 unrelated) cases, respectively. PCDH19 mutations were associated with psychiatric comorbidities in approximately 60% of females, 80% of affected mosaic males, and reported in nine hemizygous males. Hyperactive, autistic, and obsessive-compulsive features were most frequently reported. There were no genotype-phenotype associations in the individuals with recurrent variants or the group overall. Age at seizure onset can be used to provide more informative prognostic counseling.
DOI: 10.1038/s41380-018-0066-9
ORCID: 0000-0001-6247-5544
Journal: Molecular psychiatry
PubMed URL: 29892053
Type: Journal Article
Appears in Collections:Journal articles

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