title: Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome.
abstract: The clinical use of array comparative genomic hybridization in the evaluation of patients with multiple congenital anomalies and/or mental retardation has recently led to the discovery of a number of novel microdeletion and microduplication syndromes. We present four male patients with overlapping molecularly defined de novo microdeletions of 16q24.3. The clinical features observed in these patients include facial dysmorphisms comprising prominent forehead, large ears, smooth philtrum, pointed chin and wide mouth, variable cognitive impairment, autism spectrum disorder, structural anomalies of the brain, seizures and neonatal thrombocytopenia. Although deletions vary in size, the common region of overlap is only 90 kb and comprises two known genes, Ankyrin Repeat Domain 11 (ANKRD11) (MIM 611192) and Zinc Finger 778 (ZNF778), and is located approximately 10 kb distally to Cadherin 15 (CDH15) (MIM 114019). This region is not found as a copy number variation in controls. We propose that these patients represent a novel and distinctive microdeletion syndrome, characterized by autism spectrum disorder, variable cognitive impairment, facial dysmorphisms and brain abnormalities. We suggest that haploinsufficiency of ANKRD11 and/or ZNF778 contribute to this phenotype and speculate that further investigation of non-deletion patients who have features suggestive of this 16q24.3 microdeletion syndrome might uncover other mutations in one or both of these genes.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen 6500 HB, The Netherlands. m.willemsen@antrg.umcn.nl
authors.forename: Marjolein H
authors.initials: MH
authors.lastname: Willemsen
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Fernandez
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bacino
authors.forename: Erica
authors.initials: E
authors.lastname: Gerkes
authors.forename: Arjan P M
authors.initials: AP
authors.lastname: de Brouwer
authors.forename: Rolph
authors.initials: R
authors.lastname: Pfundt
authors.forename: Birgit
authors.initials: B
authors.lastname: Sikkema-Raddatz
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: Christian R
authors.initials: CR
authors.lastname: Marshall
authors.forename: Lorraine
authors.initials: L
authors.lastname: Potocki
authors.forename: Hans
authors.initials: H
authors.lastname: van Bokhoven
authors.forename: Tjitske
authors.initials: T
authors.lastname: Kleefstra
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D001321:Autistic Disorder; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics*; D013577:Syndrome; D055815:Young Adult; D016335:Zinc Fingers
chemical_list: C492515:ANKRD11 protein, human; D012097:Repressor Proteins