Journal Article

Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome

Bacino, Carlos A, Marshall, Christian R, Pfundt, Rolph, Scherer, Stephen W, Potocki, Lorraine, de Brouwer, Arjan PM, van Bokhoven, Hans, Sikkema-Raddatz, Birgit, Willemsen, Marjolein H, Fernandez, Bridget A, Gerkes, Erica, Kleefstra, Tjitske

2010

Overview

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 ZNF 778 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.

• Publisher: Springer International Publishing,Nature Publishing Group
• Subject: Abnormalities, Multiple - genetics / Adult / Autistic Disorder / Bioinformatics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Child / Child clinical studies / Child, Preschool / Chromosome Deletion / Chromosomes, Human, Pair 16 - genetics / Cognition Disorders - genetics / Comparative Genomic Hybridization / Cytogenetics / Developmental disorders / Fundamental and applied biological sciences. Psychology / Gene Expression / General aspects. Genetic counseling / Genetics of eukaryotes. Biological and molecular evolution / Human Genetics / Humans / In Situ Hybridization, Fluorescence / Infantile autism / Male / Medical genetics / Medical sciences / Molecular and cellular biology / Nucleic Acid Hybridization / Oligonucleotide Array Sequence Analysis / Phenotype / Psychology. Psychoanalysis. Psychiatry / Psychopathology. Psychiatry / Repressor Proteins - genetics / Syndrome / Young Adult / Zinc Fingers