TY - JOUR T1 - <em>FOXP1</em>-related intellectual disability syndrome: a recognisable entity JF - Journal of Medical Genetics JO - J Med Genet SP - 613 LP - 623 DO - 10.1136/jmedgenet-2017-104579 VL - 54 IS - 9 AU - Ilse Meerschaut AU - Daniel Rochefort AU - Nicole Revençu AU - Justine Pètre AU - Christina Corsello AU - Guy A Rouleau AU - Fadi F Hamdan AU - Jacques L Michaud AU - Jenny Morton AU - Jessica Radley AU - Nicola Ragge AU - Sixto García-Miñaúr AU - Pablo Lapunzina AU - Maria Palomares Bralo AU - Maria Ángeles Mori AU - Stéphanie Moortgat AU - Valérie Benoit AU - Sandrine Mary AU - Nele Bockaert AU - Ann Oostra AU - Olivier Vanakker AU - Milen Velinov AU - Thomy JL de Ravel AU - Djalila Mekahli AU - Jonathan Sebat AU - Keith K Vaux AU - Nataliya DiDonato AU - Andrea K Hanson-Kahn AU - Louanne Hudgins AU - Bruno Dallapiccola AU - Antonio Novelli AU - Luigi Tarani AU - Joris Andrieux AU - Michael J Parker AU - Katherine Neas AU - Berten Ceulemans AU - An-Sofie Schoonjans AU - Darina Prchalova AU - Marketa Havlovicova AU - Miroslava Hancarova AU - Magdalena Budisteanu AU - Annelies Dheedene AU - Björn Menten AU - Patrick A Dion AU - Damien Lederer AU - Bert Callewaert Y1 - 2017/09/01 UR - http://jmg.bmj.com/content/54/9/613.abstract N2 - Background Mutations in forkhead box protein P1 (FOXP1) cause intellectual disability (ID) and specific language impairment (SLI), with or without autistic features (MIM: 613670). Despite multiple case reports no specific phenotype emerged so far.Methods We correlate clinical and molecular data of 25 novel and 23 previously reported patients with FOXP1 defects. We evaluated FOXP1 activity by an in vitro luciferase model and assessed protein stability in vitro by western blotting.Results Patients show ID, SLI, neuromotor delay (NMD) and recurrent facial features including a high broad forehead, bent downslanting palpebral fissures, ptosis and/or blepharophimosis and a bulbous nasal tip. Behavioural problems and autistic features are common. Brain, cardiac and urogenital malformations can be associated. More severe ID and NMD, sensorineural hearing loss and feeding difficulties are more common in patients with interstitial 3p deletions (14 patients) versus patients with monogenic FOXP1 defects (34 patients). Mutations result in impaired transcriptional repression and/or reduced protein stability.Conclusions FOXP1-related ID syndrome is a recognisable entity with a wide clinical spectrum and frequent systemic involvement. Our data will be helpful to evaluate genotype–phenotype correlations when interpreting next-generation sequencing data obtained in patients with ID and/or SLI and will guide clinical management. ER -