title: Filamin A mutations cause periventricular heterotopia with Ehlers-Danlos syndrome.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Neurogenetics, Department of Neurology, Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: V L
authors.initials: VL
authors.lastname: Sheen
authors.forename: A
authors.initials: A
authors.lastname: Jansen
authors.forename: M H
authors.initials: MH
authors.lastname: Chen
authors.forename: E
authors.initials: E
authors.lastname: Parrini
authors.forename: T
authors.initials: T
authors.lastname: Morgan
authors.forename: R
authors.initials: R
authors.lastname: Ravenscroft
authors.forename: V
authors.initials: V
authors.lastname: Ganesh
authors.forename: T
authors.initials: T
authors.lastname: Underwood
authors.forename: J
authors.initials: J
authors.lastname: Wiley
authors.forename: R
authors.initials: R
authors.lastname: Leventer
authors.forename: R R
authors.initials: RR
authors.lastname: Vaid
authors.forename: D E
authors.initials: DE
authors.lastname: Ruiz
authors.forename: G M
authors.initials: GM
authors.lastname: Hutchins
authors.forename: J
authors.initials: J
authors.lastname: Menasha
authors.forename: J
authors.initials: J
authors.lastname: Willner
authors.forename: Y
authors.initials: Y
authors.lastname: Geng
authors.forename: K W
authors.initials: KW
authors.lastname: Gripp
authors.forename: L
authors.initials: L
authors.lastname: Nicholson
authors.forename: E
authors.initials: E
authors.lastname: Berry-Kravis
authors.forename: A
authors.initials: A
authors.lastname: Bodell
authors.forename: K
authors.initials: K
authors.lastname: Apse
authors.forename: R S
authors.initials: RS
authors.lastname: Hill
authors.forename: F
authors.initials: F
authors.lastname: Dubeau
authors.forename: F
authors.initials: F
authors.lastname: Andermann
authors.forename: J
authors.initials: J
authors.lastname: Barkovich
authors.forename: E
authors.initials: E
authors.lastname: Andermann
authors.forename: Y Y
authors.initials: YY
authors.lastname: Shugart
authors.forename: P
authors.initials: P
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Viri
authors.forename: P
authors.initials: P
authors.lastname: Veggiotti
authors.forename: S
authors.initials: S
authors.lastname: Robertson
authors.forename: R
authors.initials: R
authors.lastname: Guerrini
authors.forename: C A
authors.initials: CA
authors.lastname: Walsh
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D001921:Brain / Q000002:abnormalities*; D002648:Child; D041321:Chromosomes, Human, X / Q000235:genetics; D003285:Contractile Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D004252:DNA Mutational Analysis; D004535:Ehlers-Danlos Syndrome / Q000235:genetics* / Q000473:pathology; D004827:Epilepsy / Q000209:etiology; D005091:Exons / Q000235:genetics; D005260:Female; D064448:Filamins; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008840:Microfilament Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D018895:Microsatellite Repeats; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins