Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/119632
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Type: Journal article
Title: A systematic review and meta-analysis of 271 PCDH19-variant individuals identifies psychiatric comorbidities, and association of seizure onset and disease severity
Author: Kolc, K.
Sadleir, L.
Scheffer, I.
Ivancevic, A.
Roberts, R.
Pham, D.
Gecz, J.
Citation: Molecular Psychiatry, 2018; 24(2):241-251
Publisher: Springer Nature
Issue Date: 2018
ISSN: 1359-4184
1476-5578
Statement of
Responsibility: 
Kristy L Kolc, Lynette G Sadleir, Ingrid E Scheffer, Atma Ivancevic, Rachel Roberts, Duyen H Pham, Jozef Gecz
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.
Keywords: Humans; Epilepsy; Spasms, Infantile; Seizures; Cadherins; Comorbidity; Mutation; Infant; Infant, Newborn; Female; Male; Genetic Association Studies; Intellectual Disability
Rights: © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
RMID: 0030090675
DOI: 10.1038/s41380-018-0066-9
Grant ID: http://purl.org/au-research/grants/nhmrc/1091593
http://purl.org/au-research/grants/nhmrc/1041920
Appears in Collections:Medicine publications

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