title: Further delineation of the 17p13.3 microdeletion involving YWHAE but distal to PAFAH1B1: four additional patients.
abstract: BACKGROUND
  The 17p13.3 deletion syndrome (or Miller-Dieker syndrome, MDS, MIM 247200) is characterized by lissencephaly, mental retardation and facial dysmorphism. The phenotype is attributed to haploinsufficiency of two genes present in the minimal critical region of MDS: PAFAH1B1 (formerly referred to as LIS1) and YWHAE. Whereas isolated PAFAH1B1 deletion causes lissencephaly, YWHAE is a candidate for the dysmorphic phenotype associated with MDS.
  
  
  OBJECTIVE
  We describe clinical, neuroradiological and molecular data in four patients with a 17p13.3 deletion distal to PAFAH1B1 involving YWHAE.
  
  
  RESULTS
  All patients presented with mild or moderate developmental delay and pre and/or post-natal growth retardation. Patients A, B and C had neuro-imaging anomalies: leucoencephalopathy with macrocephaly (patients A and C), Chiari type 1 malformation (patient A) and paraventricular cysts (patient C). Patient B had patent ductus arteriosus and pulmonary arterial hypertension. Patient C had unilateral club foot. Patient D had enlarged Virchow Robin spaces, microcornea, and chorioretinal and lens coloboma. Array-CGH revealed de novo terminal 17p13.3 deletions for patient A and B, and showed interstitial 17p13.3 deletions of 1.4 Mb for patient C and of 0.5 Mb for patient D. In all patients, PAFAH1B1 was not deleted.
  
  
  CONCLUSIONS
  Our patients confirm that 17p deletion distal to PAFAH1B1 have a distinctive phenotype : mild mental retardation, moderate to severe growth restriction, white matter abnormalities and developmental defects including Chiari type 1 malformation and coloboma. Our patients contribute to the delineation and clinical characterization of 17p13.3 deletion distal to PAFAH1B1 and highlight the role of the region containing YWHAE in brain and eye development and in somatic growth.
authors.affiliation: Department of Pediatric Neurology & Metabolic Diseases, APHP-Robert DEBRE University Hospital, Paris, France.
authors.forename: Manuel
authors.initials: M
authors.lastname: Schiff
authors.forename: Andrée
authors.initials: A
authors.lastname: Delahaye
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
authors.forename: Damien
authors.initials: D
authors.lastname: Sanlaville
authors.forename: Catherine
authors.initials: C
authors.lastname: Vincent-Delorme
authors.forename: Azzedine
authors.initials: A
authors.lastname: Aboura
authors.forename: Brigitte
authors.initials: B
authors.lastname: Benzacken
authors.forename: Sonia
authors.initials: S
authors.lastname: Bouquillon
authors.forename: Monique
authors.initials: M
authors.lastname: Elmaleh-Berges
authors.forename: Audrey
authors.initials: A
authors.lastname: Labalme
authors.forename: Sandrine
authors.initials: S
authors.lastname: Passemard
authors.forename: Laurence
authors.initials: L
authors.lastname: Perrin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Manouvrier-Hanu
authors.forename: Patrick
authors.initials: P
authors.lastname: Edery
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.forename: Séverine
authors.initials: S
authors.lastname: Drunat
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics* / Q000378:metabolism; D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism; D000015:Abnormalities, Multiple / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics* / Q000378:metabolism; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000235:genetics*; D005260:Female; D057895:Haploinsufficiency; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D048948:14-3-3 Proteins; D008869:Microtubule-Associated Proteins; C482983:YWHAE protein, human; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human