title: Extending the phenotype of recurrent rearrangements of 16p11.2: deletions in mentally retarded patients without autism and in normal individuals.
abstract: Array CGH (comparative genomic hybridization) screening of large patient cohorts with mental retardation and/or multiple congenital anomalies (MR/MCA) has led to the identification of a number of new microdeletion and microduplication syndromes. Recently, a recurrent copy number variant (CNV) at chromosome 16p11.2 was reported to occur in up to 1% of autistic patients in three large autism studies. In the screening of 4284 patients with MR/MCA with various array platforms, we detected 22 individuals (14 index patients and 8 family members) with deletions in 16p11.2, which are genomically identical to those identified in the autism studies. Though some patients shared a facial resemblance and a tendency to overweight, there was no evidence for a recognizable phenotype. Autism was not the presenting feature in our series. The assembled evidence indicates that recurrent 16p11.2 deletions are associated with variable clinical outcome, most likely arising from haploinsufficiency of one or more genes. The phenotypical spectrum ranges from MR and/or MCA, autism, learning and speech problems, to a normal phenotype.
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. e.k.bijlsma@lumc.nl
authors.forename: E K
authors.initials: EK
authors.lastname: Bijlsma
authors.forename: A C J
authors.initials: AC
authors.lastname: Gijsbers
authors.forename: J H M
authors.initials: JH
authors.lastname: Schuurs-Hoeijmakers
authors.forename: A
authors.initials: A
authors.lastname: van Haeringen
authors.forename: D E
authors.initials: DE
authors.lastname: Fransen van de Putte
authors.forename: B-M
authors.initials: BM
authors.lastname: Anderlid
authors.forename: J
authors.initials: J
authors.lastname: Lundin
authors.forename: P
authors.initials: P
authors.lastname: Lapunzina
authors.forename: L A
authors.initials: LA
authors.lastname: Pérez Jurado
authors.forename: B
authors.initials: B
authors.lastname: Delle Chiaie
authors.forename: B
authors.initials: B
authors.lastname: Loeys
authors.forename: B
authors.initials: B
authors.lastname: Menten
authors.forename: A
authors.initials: A
authors.lastname: Oostra
authors.forename: H
authors.initials: H
authors.lastname: Verhelst
authors.forename: D J
authors.initials: DJ
authors.lastname: Amor
authors.forename: D L
authors.initials: DL
authors.lastname: Bruno
authors.forename: A J
authors.initials: AJ
authors.lastname: van Essen
authors.forename: R
authors.initials: R
authors.lastname: Hordijk
authors.forename: B
authors.initials: B
authors.lastname: Sikkema-Raddatz
authors.forename: K T
authors.initials: KT
authors.lastname: Verbruggen
authors.forename: M C J
authors.initials: MC
authors.lastname: Jongmans
authors.forename: R
authors.initials: R
authors.lastname: Pfundt
authors.forename: H M
authors.initials: HM
authors.lastname: Reeser
authors.forename: M H
authors.initials: MH
authors.lastname: Breuning
authors.forename: C A L
authors.initials: CA
authors.lastname: Ruivenkamp
mesh_terms: D000015:Abnormalities, Multiple; D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002885:Chromosomes, Human, Pair 16; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D007859:Learning Disabilities; D008297:Male; D013064:Speech Disorders; D055815:Young Adult