Journal of Medical Genetics 2007;44:791-796
LETTERS TO JMG
Deletions or duplications in KCNQ2 can cause benign familial neonatal seizures
1 Department of Genetic Medicine, Womens and Childrens Hospital, North Adelaide, South Australia, Australia
2 School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia
3 Department of Medicine (Neurology), University of Melbourne and Austin Health, Heidelberg, Victoria, Australia
4 Fraser of Allander Neurosciences Unit, Royal Hospital for Sick Children, Yorkhill, Glasgow, UK
5 Schneider Childrens Medical Center, Petaq Tikva, Israel
6 Department of Neurology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
7 Department of Paediatrics, University of Melbourne, Royal Childrens Hospital, Melbourne, Victoria, Australia
8 School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia
Ms S Heron, Department of Genetic Medicine, Womens and Childrens Hospital, 72 King William Road, North Adelaide SA 5006, Australia; sarah.heron{at}cywhs.sa.gov.au
Background: Benign familial neonatal seizures are most often caused by mutations in the voltage-gated potassium channel subunit gene KCNQ2. More than 60 mutations have been described in BFNS families, approximately half of which lead to protein truncation. The hypothesis of this study was that deletion or duplication of
1 exons of KCNQ2 could cause BFNS in cases without coding or splicing mutations.
Methods: Multiplex ligation-dependent probe amplification (MLPA) was used to test a group of 21 unrelated patients with clinical features consistent with either BFNS, benign familial neonatal–infantile seizures or sporadic neonatal seizures, for exonic deletions and duplications.
Results: Three deletions and one duplication mutation were identified in four familial cases and cascade testing of their available family members showed that the mutations segregated with the phenotype in each family. The junction fragment for one of the deletions was amplified by PCR and sequenced to characterise the breakpoint and verify that a deletion had occurred.
Conclusions: Submicroscopic deletions or duplications of KCNQ2 are seen in a significant proportion of BFNS families: four of nine (44%) cases previously testing negative for coding or splice site mutation by sequencing KCNQ2 and KCNQ3. MLPA is an efficient second-tier testing strategy for KCNQ2 to identify pathogenic intragenic mutations not detectable by conventional DNA sequencing methods.
Abbreviations: BFNIS, benign familial neonatal-infantile seizures; BFNS, benign familial neonatal seizures; MLPA, multiplex ligation-dependent probe amplification; OMIM, Online Mendelian Inheritance in Man
Keywords: neonatal seizures; deletion; duplication; epilepsy; potassium channel; MLPA
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
-
Kurahashi, H., Wang, J. -w., Ishii, A., Kojima, T., Wakai, S., Kizawa, T., Fujimoto, Y., Kikkawa, K., Yoshimura, K., Inoue, T., Yasumoto, S., Ogawa, A., Kaneko, S., Hirose, S.
(2009). Deletions involving both KCNQ2 and CHRNA4 present with benign familial neonatal seizures. Neurology
73: 1214-1217
[Abstract] [Full Text] -
Maljevic, S., Wuttke, T. V., Lerche, H.
(2008). Nervous system KV7 disorders: breakdown of a subthreshold brake. J. Physiol.
586: 1791-1801
[Abstract] [Full Text]
Register for free content
The full back archive is now available for all BMJ Journals. Institutional subscribers may access the entire archive as part of their subscription. Personal subscribers will also have access to all content when logged in. Non-subscribers who register have free access to all articles published before 2006 right back to volume 1 issue 1. Register here to access the free archive of all BMJ Journals.
Don't forget to sign up for content alerts so you keep up to date with all the articles as they are published.
