PT - JOURNAL ARTICLE AU - Margaret J Wat AU - Victoria B Enciso AU - Wojciech Wiszniewski AU - Trevor Resnick AU - Patricia Bader AU - Elizabeth R Roeder AU - Debra Freedenberg AU - Chester Brown AU - Pawel Stankiewicz AU - Sau-Wai Cheung AU - Daryl A Scott TI - Recurrent microdeletions of 15q25.2 are associated with increased risk of congenital diaphragmatic hernia, cognitive deficits and possibly Diamond–Blackfan anaemia AID - 10.1136/jmg.2009.075903 DP - 2010 Nov 01 TA - Journal of Medical Genetics PG - 777--781 VI - 47 IP - 11 4099 - http://jmg.bmj.com/content/47/11/777.short 4100 - http://jmg.bmj.com/content/47/11/777.full SO - J Med Genet2010 Nov 01; 47 AB - Background Congenital diaphragmatic hernia (CDH) can occur in isolation or in association with other abnormalities. We hypothesised that some cases of non-isolated CDH are caused by novel genomic disorders.Methods and results In a cohort of >12 000 patients referred for array comparative genomic hybridisation testing, we identified three individuals—two of whom had CDH—with deletions involving a ∼2.3 Mb region on chromosome 15q25.2. Two additional patients with deletions of this region have been reported, including a fetus with CDH. Clinical data from these patients suggest that recurrent deletions of 15q25.2 are associated with an increased risk of developing CDH, cognitive deficits, cryptorchidism, short stature and possibly Diamond–Blackfan anaemia (DBA). Although no known CDH-associated genes are located on 15q25.2, four genes in this region—CPEB1, AP3B2, HOMER2 and HDGFRP3—have been implicated in CNS development/function and may contribute to the cognitive deficits seen in deletion patients. Deletions of RPS17 may also predispose individuals with 15q25.2 deletions to DBA and associated anomalies.Conclusions Individuals with recurrent deletions of 15q25.2 are at increased risk for CDH and other birth defects. A high index of suspicion should exist for the development of cognitive defects, anaemia and DBA-associated malignancies in these individuals.