Identification of genomic deletions spanning the PCDH19 gene in two unrelated girls with intellectual disability and seizures

A. K. Vincent, A. Noor, A. Janson, B. A. Minassian, M. Ayub, J. B. Vincent, C. F. Morel

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)540-545
Number of pages6
JournalClinical Genetics
Volume82
Issue number6
DOIs
StatePublished - Dec 1 2012

Fingerprint

Intellectual Disability
Seizures
Genes
X-Linked Genes
Missense Mutation
Cadherins
Phenotype
Brain
Proteins

Keywords

  • Cadherins
  • EFMR
  • Intellectual disability (ID)
  • PCDH19
  • X-linked disorder
  • Xq21.33-q22.1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Identification of genomic deletions spanning the PCDH19 gene in two unrelated girls with intellectual disability and seizures. / Vincent, A. K.; Noor, A.; Janson, A.; Minassian, B. A.; Ayub, M.; Vincent, J. B.; Morel, C. F.

In: Clinical Genetics, Vol. 82, No. 6, 01.12.2012, p. 540-545.

Research output: Contribution to journalArticle

Vincent, A. K. ; Noor, A. ; Janson, A. ; Minassian, B. A. ; Ayub, M. ; Vincent, J. B. ; Morel, C. F. / Identification of genomic deletions spanning the PCDH19 gene in two unrelated girls with intellectual disability and seizures. In: Clinical Genetics. 2012 ; Vol. 82, No. 6. pp. 540-545.
@article{825ea6573e184a09bdc64cee95580b83,
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.",
keywords = "Cadherins, EFMR, Intellectual disability (ID), PCDH19, X-linked disorder, Xq21.33-q22.1",
author = "Vincent, {A. K.} and A. Noor and A. Janson and Minassian, {B. A.} and M. Ayub and Vincent, {J. B.} and Morel, {C. F.}",
year = "2012",
month = "12",
day = "1",
doi = "10.1111/j.1399-0004.2011.01812.x",
language = "English (US)",
volume = "82",
pages = "540--545",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Identification of genomic deletions spanning the PCDH19 gene in two unrelated girls with intellectual disability and seizures

AU - Vincent, A. K.

AU - Noor, A.

AU - Janson, A.

AU - Minassian, B. A.

AU - Ayub, M.

AU - Vincent, J. B.

AU - Morel, C. F.

PY - 2012/12/1

Y1 - 2012/12/1

N2 - 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.

AB - 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.

KW - Cadherins

KW - EFMR

KW - Intellectual disability (ID)

KW - PCDH19

KW - X-linked disorder

KW - Xq21.33-q22.1

UR - http://www.scopus.com/inward/record.url?scp=84869092276&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84869092276&partnerID=8YFLogxK

U2 - 10.1111/j.1399-0004.2011.01812.x

DO - 10.1111/j.1399-0004.2011.01812.x

M3 - Article

VL - 82

SP - 540

EP - 545

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

IS - 6

ER -