FOXP1-related intellectual disability syndrome: A recognisable entity

Ilse Meerschaut, Daniel Rochefort, Nicole Revençu, Justine Pètre, Christina Corsello, Guy A. Rouleau, Fadi F. Hamdan, Jacques L. Michaud, Jenny Morton, Jessica Radley, Nicola Ragge, Sixto García-Miñaúr, Pablo Lapunzina, Maria Palomares Bralo, Maria Angeles Mori, Stéphanie Moortgat, Valérie Benoit, Sandrine Mary, Nele Bockaert, Ann OostraOlivier Vanakker, Milen Velinov, Thomy J.L. De Ravel, Djalila Mekahli, Jonathan Sebat, Keith K. Vaux, Nataliya DiDonato, Andrea K. Hanson-Kahn, Louanne Hudgins, Bruno Dallapiccola, Antonio Novelli, Luigi Tarani, Joris Andrieux, Michael J. Parker, Katherine Neas, Berten Ceulemans, An Sofie Schoonjans, Darina Prchalova, Marketa Havlovicova, Miroslava Hancarova, Magdalena Budisteanu, Annelies Dheedene, Björn Menten, Patrick A. Dion, Damien Lederer, Bert Callewaert

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)613-623
Number of pages11
JournalJournal of Medical Genetics
Volume54
Issue number9
DOIs
Publication statusPublished - Sep 1 2017

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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