RT Journal Article SR Electronic T1 De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 850 OP 858 DO 10.1136/jmedgenet-2016-103909 VO 53 IS 12 A1 Iris M de Lange A1 Katherine L Helbig A1 Sarah Weckhuysen A1 Rikke S Møller A1 Milen Velinov A1 Natalia Dolzhanskaya A1 Eric Marsh A1 Ingo Helbig A1 Orrin Devinsky A1 Sha Tang A1 Heather C Mefford A1 Candace T Myers A1 Wim van Paesschen A1 Pasquale Striano A1 Koen van Gassen A1 Marjan van Kempen A1 Carolien G F de Kovel A1 Juliette Piard A1 Berge A Minassian A1 Marjan M Nezarati A1 André Pessoa A1 Aurelia Jacquette A1 Bridget Maher A1 Simona Balestrini A1 Sanjay Sisodiya A1 Marie Therese Abi Warde A1 Anne De St Martin A1 Jamel Chelly A1 EuroEPINOMICS-RES MAE working group A1 Ruben van ‘t Slot A1 Lionel Van Maldergem A1 Eva H Brilstra A1 Bobby P C Koeleman YR 2016 UL http://jmg.bmj.com/content/53/12/850.abstract AB Background Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellectual disability and epilepsy.Methods Reported females were selected for genetic testing because of substantial developmental problems and/or epilepsy. X-inactivation and expression studies were performed when possible.Results All mutations were predicted to result in a frameshift or premature stop. 12 out of 14 patients had intractable epilepsy with myoclonic and/or absence seizures, and generalised in 11. Thirteen patients had mild to severe intellectual disability. This female phenotype partially overlaps with the reported male phenotype which consists of more severe intellectual disability, microcephaly, growth retardation, facial dysmorphisms and, less frequently, epilepsy. One female patient showed completely skewed X-inactivation, complete absence of RNA expression in blood and a phenotype similar to male patients. In the six other tested patients, X-inactivation was random, confirmed by a non-significant twofold to threefold decrease of RNA expression in blood, consistent with the expected mosaicism between cells expressing mutant or normal KIAA2022 alleles.Conclusions Heterozygous loss of KIAA2022 expression is a cause of intellectual disability in females. Compared with its hemizygous male counterpart, the heterozygous female disease has less severe intellectual disability, but is more often associated with a severe and intractable myoclonic epilepsy.