Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity

• Published in: Genetics in medicine Vol. 12; no. 10; pp. 641 - 647
• Main Authors: Bachmann-Gagescu, Ruxandra, Mefford, Heather C., Cowan, Charles, Glew, Gwen M., Hing, Anne V., Wallace, Stephanie, Bader, Patricia I., Hamati, Aline, Reitnauer, Pamela J., Smith, Rosemarie, Stockton, David W., Muhle, Hiltrud, Helbig, Ingo, Eichler, Evan E., Ballif, Blake C., Rosenfeld, Jill, Tsuchiya, Karen D.
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.10.2010; Nature Publishing Group US
• Subjects: 16p11.2; Abnormalities, Multiple - genetics; Adaptor Proteins, Signal Transducing - genetics; Autism; Biomedical and Life Sciences; Biomedicine; Body mass; Body Mass Index; Child, Preschool; chromosome 16; Chromosomes, Human, Pair 16 - genetics; Comparative Genomic Hybridization; Congenital defects; developmental delay; Developmental Disabilities - genetics; DNA Copy Number Variations; Gene deletion; Gene Dosage; Genetics; Genome-Wide Association Study; Genomes; genomics; Handicapped; Handicapped (mentally); Human Genetics; Humans; Infant; Infant, Newborn; Intellectual Disability - genetics; Laboratory Medicine; Mental disorders; Mental illness; Mental retardation; microdeletion; Nucleic Acid Hybridization; Obesity; Obesity - genetics; Patients; Phenotype; Schizophrenia; Segmental Duplications, Genomic; Sequence Deletion; SH2B1; developmental delay; microdeletion; obesity; 16p11.2; SH2B1
• ISSN: 1098-3600; 1530-0366
• DOI: 10.1097/GIM.0b013e3181ef4286

The short arm of chromosome 16 is rich in segmental duplications, predisposing this region of the genome to a number of recurrent rearrangements. Genomic imbalances of an approximately 600-kb region in 16p11.2 (29.5–30.1 Mb) have been associated with autism, intellectual disability, congenital anomalies, and schizophrenia. However, a separate, distal 200-kb region in 16p11.2 (28.7–28.9 Mb) that includes the SH2B1 gene has been recently associated with isolated obesity. The purpose of this study was to better define the phenotype of this recurrent SH2B1-containing microdeletion in a cohort of phenotypically abnormal patients not selected for obesity. Array comparative hybridization was performed on a total of 23,084 patients in a clinical setting for a variety of indications, most commonly developmental delay. Deletions of the SH2B1-containing region were identified in 31 patients. The deletion is enriched in the patient population when compared with controls (P = 0.003), with both inherited and de novo events. Detailed clinical information was available for six patients, who all had developmental delays of varying severity. Body mass index was ≥95th percentile in four of six patients, supporting the previously described association with obesity. The reciprocal duplication, found in 17 patients, does not seem to be significantly enriched in our patient population compared with controls. Deletions of the 16p11.2 SH2B1-containing region are pathogenic and are associated with developmental delay in addition to obesity.