RT Journal Article
SR Electronic
T1 <em>FOXP1</em>-related intellectual disability syndrome: a recognisable entity
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 613
OP 623
DO 10.1136/jmedgenet-2017-104579
VO 54
IS 9
A1 Ilse Meerschaut
A1 Daniel Rochefort
A1 Nicole Revençu
A1 Justine Pètre
A1 Christina Corsello
A1 Guy A Rouleau
A1 Fadi F Hamdan
A1 Jacques L Michaud
A1 Jenny Morton
A1 Jessica Radley
A1 Nicola Ragge
A1 Sixto García-Miñaúr
A1 Pablo Lapunzina
A1 Maria Palomares Bralo
A1 Maria Ángeles Mori
A1 Stéphanie Moortgat
A1 Valérie Benoit
A1 Sandrine Mary
A1 Nele Bockaert
A1 Ann Oostra
A1 Olivier Vanakker
A1 Milen Velinov
A1 Thomy JL de Ravel
A1 Djalila Mekahli
A1 Jonathan Sebat
A1 Keith K Vaux
A1 Nataliya DiDonato
A1 Andrea K Hanson-Kahn
A1 Louanne Hudgins
A1 Bruno Dallapiccola
A1 Antonio Novelli
A1 Luigi Tarani
A1 Joris Andrieux
A1 Michael J Parker
A1 Katherine Neas
A1 Berten Ceulemans
A1 An-Sofie Schoonjans
A1 Darina Prchalova
A1 Marketa Havlovicova
A1 Miroslava Hancarova
A1 Magdalena Budisteanu
A1 Annelies Dheedene
A1 Björn Menten
A1 Patrick A Dion
A1 Damien Lederer
A1 Bert Callewaert
YR 2017
UL http://jmg.bmj.com/content/54/9/613.abstract
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.