title: Bilateral periventricular heterotopias in an X-linked dominant transmission in a family with two affected males.
abstract: We report on the case of dizygotic twin boys, born prematurely to an asymptomatic mother. Bilateral periventricular heterotopias with enlarged ventricles were discovered at birth in both twins. One of the twins died prematurely of bronchopulmonary complications, and was shown to have several neuropathological anomalies (microgyria, thin corpus callosum, and reduced white matter). The surviving twin had mental retardation, without epilepsy. MRI of the mother showed asymptomatic periventricular heterotopias without ventricular enlargement. She had two affected daughters also with asymptomatic periventricular heterotopias. A point mutation in the last coding exon 48 of the Filamin A (FLNA) gene (7922c > t) was discovered on sequencing and segregated with the affected individuals. This family has a classical X-linked dominant BPNH pathology, with greater severity in males than females. The location of the FLNA mutation is discussed in light of the neuropathological anomalies and mental retardation in male patients.
authors.affiliation: Medical genetics, Hôpital Robert Debré, Paris, France. marion.gerard@rdb.aphp.fr
authors.forename: Marion
authors.initials: M
authors.lastname: Gérard-Blanluet
authors.forename: Volney
authors.initials: V
authors.lastname: Sheen
authors.forename: Kalotina
authors.initials: K
authors.lastname: Machinis
authors.forename: Jason
authors.initials: J
authors.lastname: Neal
authors.forename: Kira
authors.initials: K
authors.lastname: Apse
authors.forename: Claude
authors.initials: C
authors.lastname: Danan
authors.forename: Martine
authors.initials: M
authors.lastname: Sinico
authors.forename: Pierre
authors.initials: P
authors.lastname: Brugières
authors.forename: Katia
authors.initials: K
authors.lastname: Mage
authors.forename: Lanto
authors.initials: L
authors.lastname: Ratsimbazafy
authors.forename: Annie
authors.initials: A
authors.lastname: Elbez
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Janaud
authors.forename: Serge
authors.initials: S
authors.lastname: Amselem
authors.forename: Christopher
authors.initials: C
authors.lastname: Walsh
authors.forename: Férechté
authors.initials: F
authors.lastname: Encha-Razavi
mesh_terms: D000595:Amino Acid Sequence; D001927:Brain Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D002552:Cerebral Ventricles; D002828:Choristoma / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003285:Contractile Proteins / Q000235:genetics*; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D064448:Filamins; D005799:Genes, Dominant / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000235:genetics; D006801:Humans; D007223:Infant; D008171:Lung Diseases / Q000150:complications; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D017386:Sequence Homology, Amino Acid; D014429:Twins, Dizygotic / Q000235:genetics
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins