Neurology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sheen, V. L.
Right arrow Articles by Walsh, C. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sheen, V. L.
Right arrow Articles by Walsh, C. A.
Related Collections
Right arrow All Epilepsy/Seizures
Right arrow Cortical dysplasia
NEUROLOGY 2005;64:254-262
© 2005 American Academy of Neurology

Filamin A mutations cause periventricular heterotopia with Ehlers-Danlos syndrome

V. L. Sheen, MD, PhD*, A. Jansen, MD*, M. H. Chen, MD, E. Parrini, PhD, T. Morgan, MSc, R. Ravenscroft, BA, V. Ganesh, BS, T. Underwood, FRACP, J. Wiley, MD, R. Leventer, FRACP, R. R. Vaid, MD, PhD, D. E. Ruiz, MD, G. M. Hutchins, MD, J. Menasha, MD, J. Willner, MD, Y. Geng, MD, K. W. Gripp, MD, L. Nicholson, MS, MC, E. Berry-Kravis, MD, A. Bodell, MS, CGC, K. Apse, ScM, R. S. Hill, PhD, F. Dubeau, MD, F. Andermann, MD, J. Barkovich, MD, E. Andermann, MD, Y. Y. Shugart, PhD, P. Thomas, MD, M. Viri, MD, P. Veggiotti, MD, S. Robertson, FRACP, Dphil, R. Guerrini, MD and C. A. Walsh, MD, PhD

From the Division of Neurogenetics (Drs. Sheen, Hill, and Walsh, and R. Ravenscroft, V. Ganesh, A. Bodell, and K. Apse), Department of Neurology, Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, Boston; Montreal Neurological Institute and Hospital (Drs. Jansen, Dubeau, and Andermann), and the Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec; Brigham and Women’s Hospital (Dr. Chen), Cardiovascular Division, Boston; Epilepsy, Neurophysiology & Neurogenetics Unit (Drs. Parrini and Guerrini), Division of Child Neurology and Psychiatry, University of Pisa & IRCCS Fondazione Stella Maris, Pisa, Italy; Department of Paediatrics and Child Health (T. Morganand Dr. Robertson), University of Otago, Dunedin, New Zealand; Departments of Hematology and Respiratory Medicine (Drs. Underwood ans Wiley), Nepean Hospital, Sydney, Australia; Department of Neurology (Dr. Leventer), Royal Children’s Hospital, & Murdoch Children’s Research Institute, University of Melbourne, Victoria, Australia; Department of Radiology (Drs. Vaid, Ruiz, and Barkovich), University of California at San Francisco; Department of Pathology (Dr. Hutchins), The Johns Hopkins Hospital, Baltimore, MD; Department of Human Genetics (Drs. Menasha, Willner, and Geng), Mount Sinai Hospital, New York, NY; Division of Medical Genetics (Dr. Gripp and L. Nicholson), duPont Hospital for Children, Wilmington, DE; Department of Pediatrics (Dr. Berry-Kravis), Section of Neurology, Rush University Medical Center, Chicago, IL; Department of Human Genetics (Dr. Andermann), McGill University, Montreal, Quebec, Canada; Department of Epidemiology (Dr. Shugart), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Service de Neurologie (Dr. Thomas), Hopital Pasteur, Nice, France; Ospedale Fatebenefratelli (Dr. Viri), Milan, Italy; Neuropsichiatria Infantile (Dr. Veggiotti), Istituto Mondino Pavia, Italy; and Program in Biological and Biomedical Sciences (Dr. Walsh), Harvard Medical School, Boston, MA.

Address correspondence and reprint requests to Dr. C.A. Walsh, Harvard Medical School, Boston, MA 02115; e-mail: cwalsh{at}bidmc.harvard.edu

Objective: To define the clinical, radiologic, and genetic features of periventricular heterotopia (PH) with Ehlers-Danlos syndrome (EDS).

Methods: Exonic sequencing and single stranded conformational polymorphism (SSCP) analysis was performed on affected individuals. Linkage analysis using microsatellite markers on the X-chromosome was performed on a single pedigree. Western blotting evaluated for loss of filamin A (FLNA) protein and Southern blotting assessed for any potential chromosome rearrangement in this region.

Results: The authors report two familial cases and nine additional sporadic cases of the EDS-variant form of PH, which is characterized by nodular brain heterotopia, joint hypermobility, and development of aortic dilatation in early adulthood. MRI typically demonstrated bilateral nodular PH, indistinguishable from PH due to FLNA mutations. Exonic sequencing or SSCP analyses of FLNA revealed a 2762 delG single base pair deletion in one affected female. Another affected female harbored a C116 single point mutation, resulting in an A39G change. A third affected female had a 4147 delG single base pair deletion. One pedigree with no detectable exonic mutation demonstrated positive linkage to the FLNA locus Xq28, an affected individual in this family also had no detectable FLNA protein, but no chromosomal rearrangement was detected.

Conclusion: These results suggest that the Ehlers-Danlos variant of periventricular heterotopia (PH), in part, represents an overlapping syndrome with X-linked dominant PH due to filamin A mutations.

*These authors contributed equally to this work.

Supported by Grant R-04–35 to R.G. from Fondazione Mariani and by grants to C.A.W. from the National Institute of Neurologic Disorders and Stroke (2R37 NS35129 and 1PO1NS40043), the March of Dimes, and the McKnight Foundation. C.A.W. is an Investigator of the Howard Hughes Medical Institute. V.L.S. is supported by a grant from the NIMH (1K08MH/NS63886–01). V.L.S. is a Charles A. Dana fellow.

Received July 28, 2004. Accepted in final form October 4, 2004.




This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
T. Lowe, R. A. Kley, P. F.M. van der Ven, M. Himmel, A. Huebner, M. Vorgerd, and D. O. Furst
The pathomechanism of filaminopathy: altered biochemical properties explain the cellular phenotype of a protein aggregation myopathy
Hum. Mol. Genet., June 1, 2007; 16(11): 1351 - 1358.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
F. Kyndt, J.-P. Gueffet, V. Probst, P. Jaafar, A. Legendre, F. Le Bouffant, C. Toquet, E. Roy, L. McGregor, S. A. Lynch, et al.
Mutations in the Gene Encoding Filamin A as a Cause for Familial Cardiac Valvular Dystrophy
Circulation, January 2, 2007; 115(1): 40 - 49.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. W. Hart, J. E. Morgan, J. Schneider, K. West, L. McKie, S. Bhattacharya, I. J. Jackson, and S. H. Cross
Cardiac malformations and midline skeletal defects in mice lacking filamin A
Hum. Mol. Genet., August 15, 2006; 15(16): 2457 - 2467.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
E. Parrini, A. Ramazzotti, W. B. Dobyns, D. Mei, F. Moro, P. Veggiotti, C. Marini, E. H. Brilstra, B. D. Bernardina, L. Goodwin, et al.
Periventricular heterotopia: phenotypic heterogeneity and correlation with Filamin A mutations
Brain, July 1, 2006; 129(7): 1892 - 1906.
[Abstract] [Full Text] [PDF]

Home page
 Clin Med ResHome page
V. L. Sheen and C. A. Walsh
Periventricular Heterotopia: New Insights into Ehlers-Danlos Syndrome
Clin. Med. Res., November 1, 2005; 3(4): 229 - 233.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by AAN Enterprises, Inc.