FLNA genomic rearrangements cause periventricular nodular heterotopia

K. R. Clapham, T. W. Yu, V. S. Ganesh, B. Barry, Y. Chan, D. Mei, E. Parrini, B. Funalot, L. Dupuis, M. M. Nezarati, C. Du Souich, C. Van Karnebeek, R. Guerrini, C. A. Walsh

Research output: Contribution to journalArticlepeer-review


Objective: To identify copy number variant (CNV) causes of periventricular nodular heterotopia (PNH) in patients for whom FLNA sequencing is negative. Methods: Screening of 35 patients from 33 pedigrees on an Affymetrix 6.0 microarray led to the identification of one individual bearing a CNV that disrupted FLNA. FLNA-disrupting CNVs were also isolated in 2 other individuals by multiplex ligation probe amplification. These 3 cases were further characterized by high-resolution oligo array comparative genomic hybridization (CGH), and the precise junctional breakpoints of the rearrangements were identified byPCRamplification and sequencing. Results: We report 3 cases of PNH caused by nonrecurrent genomic rearrangements that disrupt one copy of FLNA. The first individual carried a 113-kb deletion that removes all but the first exon of FLNA. A second patient harbored a complex rearrangement including a deletion of the 3′ end of FLNA accompanied by a partial duplication event. A third patient bore a 39-kb deletion encompassing all of FLNA and the neighboring gene EMD. High-resolution oligo array CGH of the FLNA locus suggests distinct molecular mechanisms for each of these rearrangements, and implicates nearby low copy repeats in their pathogenesis. Conclusions: These results demonstrate that FLNA is prone to pathogenic rearrangements, and highlight the importance of screening for CNVs in individuals with PNH lacking FLNA point mutations.

Original languageEnglish
Pages (from-to)269-278
Number of pages10
Issue number4
Publication statusPublished - Jan 24 2012

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)


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