title: Multiple congenital anomalies-intellectual disability (MCA-ID) and neuroblastoma in a patient harboring a de novo 14q23.1q23.3 deletion.
abstract: Neuroblastoma is the most frequent extra cranial solid tumor in infants and children. Genetic predisposition to neuroblastoma has been suspected previously due to familial cases of sporadic NB and predisposition to NB in several syndromes. Here, we report on a de novo 14q23.1-q23.3 microdeletion in a male presenting with a neuroblastoma diagnosed at 9 months, and spherocytosis, congenital heart defect, cryptorchidism, hypoplasia of corpus callosum, epilepsy, and developmental delay. Myc-associated-factor X (MAX) haploinsufficiency could be regarded as the predisposing factor to NB. Indeed 14q deletion is a recurrent somatic rearrangement in NB and MAX somatic and germline loss of function mutation have recently been described in pheochromocytoma and paraganglioma. However, MAX was expressed in the tumor of the patient we report on and, accordingly, loss of heterozygosity, mutation, or promoter methylation were excluded. In addition, we discuss the potential involvement in the clinical spectrum presented by the patient of five of the deleted genes, namely DAAM1, PLEKHG3, SPTB, AKAP5, and ARID4A.
authors.affiliation: Département de Génétique Histologie-Embryologie-Cytogénétique, Hôpital Necker-Enfants Malades, Paris, France; INSERM U781, Université Sorbonne Paris Cité, Institut IMAGINE, Paris, France.
authors.forename: Daphné
authors.initials: D
authors.lastname: Lehalle
authors.forename: Damien
authors.initials: D
authors.lastname: Sanlaville
authors.forename: Anne
authors.initials: A
authors.lastname: Guimier
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Plouvier
authors.forename: Thierry
authors.initials: T
authors.lastname: Leblanc
authors.forename: Louise
authors.initials: L
authors.lastname: Galmiche
authors.forename: Isabelle
authors.initials: I
authors.lastname: Radford
authors.forename: Serge
authors.initials: S
authors.lastname: Romana
authors.forename: Laurence
authors.initials: L
authors.lastname: Colleaux
authors.forename: Loïc
authors.initials: L
authors.lastname: de Pontual
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D002872:Chromosome Deletion; D002883:Chromosomes, Human, Pair 14; D055028:Comparative Genomic Hybridization; D019066:Facies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D009447:Neuroblastoma / Q000175:diagnosis* / Q000235:genetics*
keywords: 14q23 microdeletion; ARID4A; MAX; development; neuroblastoma