PT  - JOURNAL ARTICLE
AU  - Meerschaut, Ilse
AU  - Rochefort, Daniel
AU  - Revençu, Nicole
AU  - Pètre, Justine
AU  - Corsello, Christina
AU  - Rouleau, Guy A
AU  - Hamdan, Fadi F
AU  - Michaud, Jacques L
AU  - Morton, Jenny
AU  - Radley, Jessica
AU  - Ragge, Nicola
AU  - García-Miñaúr, Sixto
AU  - Lapunzina, Pablo
AU  - Bralo, Maria Palomares
AU  - Mori, Maria Ángeles
AU  - Moortgat, Stéphanie
AU  - Benoit, Valérie
AU  - Mary, Sandrine
AU  - Bockaert, Nele
AU  - Oostra, Ann
AU  - Vanakker, Olivier
AU  - Velinov, Milen
AU  - de Ravel, Thomy JL
AU  - Mekahli, Djalila
AU  - Sebat, Jonathan
AU  - Vaux, Keith K
AU  - DiDonato, Nataliya
AU  - Hanson-Kahn, Andrea K
AU  - Hudgins, Louanne
AU  - Dallapiccola, Bruno
AU  - Novelli, Antonio
AU  - Tarani, Luigi
AU  - Andrieux, Joris
AU  - Parker, Michael J
AU  - Neas, Katherine
AU  - Ceulemans, Berten
AU  - Schoonjans, An-Sofie
AU  - Prchalova, Darina
AU  - Havlovicova, Marketa
AU  - Hancarova, Miroslava
AU  - Budisteanu, Magdalena
AU  - Dheedene, Annelies
AU  - Menten, Björn
AU  - Dion, Patrick A
AU  - Lederer, Damien
AU  - Callewaert, Bert
TI  - <em>FOXP1</em>-related intellectual disability syndrome: a recognisable entity
AID  - 10.1136/jmedgenet-2017-104579
DP  - 2017 Sep 01
TA  - Journal of Medical Genetics
PG  - 613--623
VI  - 54
IP  - 9
4099  - http://jmg.bmj.com/content/54/9/613.short
4100  - http://jmg.bmj.com/content/54/9/613.full
SO  - J Med Genet2017 Sep 01; 54
AB  - 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.