PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Deletions of the 16p11.2 SH2B1-containing region are pathogenic and are associated with developmental delay in addition to obesity.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Deletions of the 16p11.2 SH2B1-containing region are pathogenic and are associated with developmental delay in addition to obesity.
Authors: Brooke Sadler; Gabe Haller; Lilian Antunes; Xavier Bledsoe; Jose Morcuende; Philip Giampietro; Cathleen Raggio; Nancy Miller; Yared Kidane; Carol A Wise; Ina Amarillo; Nephi Walton; Mark Seeley; Darren Johnson; Conner Jenkins; Troy Jenkins; Matthew Oetjens; R Spencer Tong; Todd E Druley; Matthew B Dobbs; Christina A Gurnett Journal: J Med Genet Date: 2019-02-25 Impact factor: 6.318
Authors: Saul A Mullen; Gemma L Carvill; Susannah Bellows; Marta A Bayly; Holger Trucks; Dennis Lal; Thoman Sander; Samuel F Berkovic; Leanne M Dibbens; Ingrid E Scheffer; Heather C Mefford Journal: Neurology Date: 2013-09-25 Impact factor: 9.910
Authors: Saurav Guha; Elliott Rees; Ariel Darvasi; Dobril Ivanov; Masashi Ikeda; Sarah E Bergen; Patrik K Magnusson; Paul Cormican; Derek Morris; Michael Gill; Sven Cichon; Jeffrey A Rosenfeld; Annette Lee; Peter K Gregersen; John M Kane; Anil K Malhotra; Marcella Rietschel; Markus M Nöthen; Franziska Degenhardt; Lutz Priebe; René Breuer; Jana Strohmaier; Douglas M Ruderfer; Jennifer L Moran; Kimberly D Chambert; Alan R Sanders; Jianxin Shi; Kenneth Kendler; Brien Riley; Tony O'Neill; Dermot Walsh; Dheeraj Malhotra; Aiden Corvin; Shaun Purcell; Pamela Sklar; Nakao Iwata; Christina M Hultman; Patrick F Sullivan; Jonathan Sebat; Shane McCarthy; Pablo V Gejman; Douglas F Levinson; Michael J Owen; Michael C O'Donovan; Todd Lencz; George Kirov Journal: JAMA Psychiatry Date: 2013-03 Impact factor: 21.596