title: Neuropathological features in a female fetus with OPHN1 deletion and cerebellar hypoplasia.
abstract: We report the case of a 33-year-old pregnant woman. The third-trimester ultrasound scan during pregnancy revealed fetal bilateral ventricular dilatation, macrosomia and a transverse diameter of the cerebellum at the 30th centile. A brain MRI scan at 31 weeks of gestation led to a diagnosis of hypoplasia of the cerebellar vermis without hemisphere abnormalities and a non compressive expansion of the cisterna magna. The fetal karyotype was 46,XX. The pregnancy was terminated and array-CGH analysis of the fetus identified a 238 kb de novo deletion on chromosome Xp12, encompassing part of OPHN1 gene. Further studies revealed a completely skewed pattern of X inactivation. OPHN1 is involved in X-linked mental retardation (XLMR) with cerebellar hypoplasia and encodes a Rho-GTPase-activating protein called oligophrenin-1, which is produced throughout the developing mouse brain and in the hippocampus and Purkinje cells of the cerebellum in adult mice. Neuropathological examination of the female fetus revealed cerebellar hypoplasia and the heterotopia of Purkinje cells at multiple sites in the white matter of the cerebellum. This condition mostly affects male fetuses in humans. We report here the first case of a de novo partial deletion of OPHN1, with radiological and neuropathological examination, in a female fetus.
authors: Hospices Civils de Lyon, Service de Génétique, F-69677 Bron, France.
authors: Delphine
authors: D
authors: Rocas
authors: Eudeline
authors: E
authors: Alix
authors: Jessica
authors: J
authors: Michel
authors: Marie-Pierre
authors: MP
authors: Cordier
authors: Audrey
authors: A
authors: Labalme
authors: Hélène
authors: H
authors: Guilbert
authors: Marianne
authors: M
authors: Till
authors: Caroline
authors: C
authors: Schluth-Bolard
authors: Pascale
authors: P
authors: de Haas
authors: Jérôme
authors: J
authors: Massardier
authors: Vincent des
authors: Vd
authors: Portes
authors: Patrick
authors: P
authors: Edery
authors: Renaud
authors: R
authors: Touraine
authors: Laurent
authors: L
authors: Guibaud
authors: Alexandre
authors: A
authors: Vasiljevic
authors: Damien
authors: D
authors: Sanlaville
mesh_terms: D000328:Adult; D002531:Cerebellum / Q000002:abnormalities* / Q000473:pathology; D002946:Cisterna Magna / Q000002:abnormalities; D003598:Cytoskeletal Proteins / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics / Q000473:pathology; D005260:Female; D005333:Fetus / Q000002:abnormalities*; D020690:GTPase-Activating Proteins / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D007621:Karyotyping; D038901:X-Linked Intellectual Disability / Q000235:genetics / Q000473:pathology; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology; D009421:Nervous System Malformations / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D011247:Pregnancy; D011689:Purkinje Cells / Q000378:metabolism; D049951:X Chromosome Inactivation
chemical_list: D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C111952:OPHN1 protein, human; C085379:rho GTPase-activating protein