title: Identification of genomic deletions spanning the PCDH19 gene in two unrelated girls with intellectual disability and seizures.
abstract: Recently, missense and truncating mutations in the gene PCDH19 have been reported to cause female-restricted epilepsy with mental retardation (EFMR). EFMR (MIM#300088) is an X-linked disorder characterized by early onset seizures and intellectual disability (ID). Interestingly, unlike typical X-linked mode of inheritance, the phenotype is restricted to females, and males are unaffected carriers. PCDH19 is highly expressed in brain, and the encoded protein belongs to the cadherin superfamily. Here we report two unrelated female patients with deletions spanning PCDH19 identified by copy number variation (CNV) analysis and validated by qPCR. In one, we have identified a 3 Mb interstitial deletion at Xq21.33-q22.1 which spans PCDH19, LOC442459 & TNMD. This patient had her first seizure at 8 months old, and also has ID and aggressive behavior. In another female patient we identified a de novo 603 kb heterozygous deletion in a female patient with fits (since 1 year of age), ID, hyperactivity and aggressive behavior. The deletion spans the entire PCDH19 gene (also TNMD, SRPX2, TSPAN6 and SYTL4). In conclusion, our results suggest that deletions at PCDH19 also cause EFMR.
authors.affiliation: Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: A K
authors.initials: AK
authors.lastname: Vincent
authors.forename: A
authors.initials: A
authors.lastname: Noor
authors.forename: A
authors.initials: A
authors.lastname: Janson
authors.forename: B A
authors.initials: BA
authors.lastname: Minassian
authors.forename: M
authors.initials: M
authors.lastname: Ayub
authors.forename: J B
authors.initials: JB
authors.lastname: Vincent
authors.forename: C F
authors.initials: CF
authors.lastname: Morel
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D046228:Microarray Analysis; D000091363:Protocadherins; D060888:Real-Time Polymerase Chain Reaction; D012640:Seizures / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D049951:X Chromosome Inactivation / Q000235:genetics
chemical_list: D015820:Cadherins; C438605:PCDH19 protein, human; D000091363:Protocadherins