title: WWOX and severe autosomal recessive epileptic encephalopathy: first case in the prenatal period.
abstract: WWOX has been recently implicated in autosomal recessive spinocerebellar ataxia type 12 (SCAR12) and severe early-onset epileptic encephalopathy (EOEE). By array comparative genomic hybridization, we identified a 0.6 Mb homozygous deletion in 16q23.1 in a fetus presenting with brain anomalies. His older sister who died at the age of 22 months from an EOEE was also homozygous for the copy number variations in 16q23.1. This deletion includes the first six exons of WWOX and results in a null genotype in homozygous patients. This family gives additional support for the implication of WWOX in severe EOEEs. We report for the first time prenatal ultrasound findings in a fetus with a WWOX-null genotype. Our study expands the range of brain abnormalities in WWOX-related EOEEs. This additional family confirms the genotype-phenotype correlation with WWOX-null alleles associated with the most severe form of WWOX-related epileptic encephalopathy with premature death.
authors.affiliation: Laboratoire de Génétique Médicale, Centre Hospitalier Universitaire de Nancy, INSERM U954, Université de Lorraine, Rue du Morvan, Vandoeuvre-les-Nancy, France.
authors.forename: Mylène
authors.initials: M
authors.lastname: Valduga
authors.affiliation: Laboratoire de Génétique Médicale, Centre Hospitalier Universitaire de Nancy, INSERM U954, Université de Lorraine, Rue du Morvan, Vandoeuvre-les-Nancy, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Philippe
authors.affiliation: Unité de Génétique Clinique, Médecine Néonatale, Maternité Régionale Universitaire, Rue du Dr Heydenreich, Nancy, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Lambert
authors.affiliation: Service de radiologie et échographie, Maternité Régionale Universitaire, Rue du Dr Heydenreich, Nancy, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Bach-Segura
authors.affiliation: Service de neuroradiologie diagnostique et thérapeutique, Centre Hospitalier Universitaire de Nancy, Rue du Morvan, Vandoeuvre-les-Nancy, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Schmitt
authors.affiliation: Laboratoire de biologie de la reproduction et du développement, Service de Foetopathologie et placentologie, Maternité Régionale Universitaire, Rue du Dr Heydenreich, Nancy, France.
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Masutti
authors.affiliation: Service de réanimation néonatale, néonatalogie, Hôpital Femme Mère Enfant, CHR Metz Thionville, Allée du château, Ars Laquenexy, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: François
authors.affiliation: Service de réanimation néonatale, néonatalogie, Hôpital Femme Mère Enfant, CHR Metz Thionville, Allée du château, Ars Laquenexy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Pinaud
authors.affiliation: Service de pédiatrie et génétique clinique, Hôpital Femme Mère Enfant, CHR Metz Thionville, Allée du château, Ars Laquenexy, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Vibert
authors.affiliation: Laboratoire de Génétique Médicale, Centre Hospitalier Universitaire de Nancy, INSERM U954, Université de Lorraine, Rue du Morvan, Vandoeuvre-les-Nancy, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Jonveaux
mesh_terms: D001927:Brain Diseases / Q000000981:diagnostic imaging* / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004827:Epilepsy / Q000000981:diagnostic imaging* / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D005808:Genes, Recessive; D056726:Genetic Association Studies; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010088:Oxidoreductases / Q000235:genetics*; D011247:Pregnancy; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D016216:Ultrasonography, Prenatal; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human