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 journalArticle

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

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Intellectual Disability
Language
Protein Stability
Blepharophimosis
Forkhead Transcription Factors
Mutation
Forehead
Sensorineural Hearing Loss
Genetic Association Studies
Eyelids
Luciferases
Nose
Western Blotting
Phenotype
Brain

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Meerschaut, I., Rochefort, D., Revençu, N., Pètre, J., Corsello, C., Rouleau, G. A., ... Callewaert, B. (2017). FOXP1-related intellectual disability syndrome: A recognisable entity. Journal of Medical Genetics, 54(9), 613-623. https://doi.org/10.1136/jmedgenet-2017-104579

FOXP1-related intellectual disability syndrome : A recognisable entity. / Meerschaut, Ilse; Rochefort, Daniel; Revençu, Nicole; Pètre, Justine; Corsello, Christina; Rouleau, Guy A.; Hamdan, Fadi F.; Michaud, Jacques L.; Morton, Jenny; Radley, Jessica; Ragge, Nicola; García-Miñaúr, Sixto; Lapunzina, Pablo; Bralo, Maria Palomares; Mori, Maria Angeles; Moortgat, Stéphanie; Benoit, Valérie; Mary, Sandrine; Bockaert, Nele; Oostra, Ann; Vanakker, Olivier; Velinov, Milen; De Ravel, Thomy J.L.; Mekahli, Djalila; Sebat, Jonathan; Vaux, Keith K.; DiDonato, Nataliya; Hanson-Kahn, Andrea K.; Hudgins, Louanne; Dallapiccola, Bruno; Novelli, Antonio; Tarani, Luigi; Andrieux, Joris; Parker, Michael J.; Neas, Katherine; Ceulemans, Berten; Schoonjans, An Sofie; Prchalova, Darina; Havlovicova, Marketa; Hancarova, Miroslava; Budisteanu, Magdalena; Dheedene, Annelies; Menten, Björn; Dion, Patrick A.; Lederer, Damien; Callewaert, Bert.

In: Journal of Medical Genetics, Vol. 54, No. 9, 01.09.2017, p. 613-623.

Research output: Contribution to journalArticle

Meerschaut, I, Rochefort, D, Revençu, N, Pètre, J, Corsello, C, Rouleau, GA, Hamdan, FF, Michaud, JL, Morton, J, Radley, J, Ragge, N, García-Miñaúr, S, Lapunzina, P, Bralo, MP, Mori, MA, Moortgat, S, Benoit, V, Mary, S, Bockaert, N, Oostra, A, Vanakker, O, Velinov, M, De Ravel, TJL, Mekahli, D, Sebat, J, Vaux, KK, DiDonato, N, Hanson-Kahn, AK, Hudgins, L, Dallapiccola, B, Novelli, A, Tarani, L, Andrieux, J, Parker, MJ, Neas, K, Ceulemans, B, Schoonjans, AS, Prchalova, D, Havlovicova, M, Hancarova, M, Budisteanu, M, Dheedene, A, Menten, B, Dion, PA, Lederer, D & Callewaert, B 2017, 'FOXP1-related intellectual disability syndrome: A recognisable entity', Journal of Medical Genetics, vol. 54, no. 9, pp. 613-623. https://doi.org/10.1136/jmedgenet-2017-104579
Meerschaut I, Rochefort D, Revençu N, Pètre J, Corsello C, Rouleau GA et al. FOXP1-related intellectual disability syndrome: A recognisable entity. Journal of Medical Genetics. 2017 Sep 1;54(9):613-623. https://doi.org/10.1136/jmedgenet-2017-104579
Meerschaut, Ilse ; Rochefort, Daniel ; Revençu, Nicole ; Pètre, Justine ; Corsello, Christina ; Rouleau, Guy A. ; Hamdan, Fadi F. ; Michaud, Jacques L. ; Morton, Jenny ; Radley, Jessica ; Ragge, Nicola ; García-Miñaúr, Sixto ; Lapunzina, Pablo ; Bralo, Maria Palomares ; Mori, Maria Angeles ; Moortgat, Stéphanie ; Benoit, Valérie ; Mary, Sandrine ; Bockaert, Nele ; Oostra, Ann ; Vanakker, Olivier ; Velinov, Milen ; De Ravel, Thomy J.L. ; Mekahli, Djalila ; Sebat, Jonathan ; Vaux, Keith K. ; DiDonato, Nataliya ; Hanson-Kahn, Andrea K. ; Hudgins, Louanne ; Dallapiccola, Bruno ; Novelli, Antonio ; Tarani, Luigi ; Andrieux, Joris ; Parker, Michael J. ; Neas, Katherine ; Ceulemans, Berten ; Schoonjans, An Sofie ; Prchalova, Darina ; Havlovicova, Marketa ; Hancarova, Miroslava ; Budisteanu, Magdalena ; Dheedene, Annelies ; Menten, Björn ; Dion, Patrick A. ; Lederer, Damien ; Callewaert, Bert. / FOXP1-related intellectual disability syndrome : A recognisable entity. In: Journal of Medical Genetics. 2017 ; Vol. 54, No. 9. pp. 613-623.
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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.",
author = "Ilse Meerschaut and Daniel Rochefort and Nicole Reven{\cc}u and Justine P{\`e}tre and Christina Corsello and Rouleau, {Guy A.} and Hamdan, {Fadi F.} and Michaud, {Jacques L.} and Jenny Morton and Jessica Radley and Nicola Ragge and Sixto Garc{\'i}a-Mi{\~n}a{\'u}r and Pablo Lapunzina and Bralo, {Maria Palomares} and Mori, {Maria Angeles} and St{\'e}phanie Moortgat and Val{\'e}rie Benoit and Sandrine Mary and Nele Bockaert and Ann Oostra and Olivier Vanakker and Milen Velinov and {De Ravel}, {Thomy J.L.} and Djalila Mekahli and Jonathan Sebat and Vaux, {Keith K.} and Nataliya DiDonato and Hanson-Kahn, {Andrea K.} and Louanne Hudgins and Bruno Dallapiccola and Antonio Novelli and Luigi Tarani and Joris Andrieux and Parker, {Michael J.} and Katherine Neas and Berten Ceulemans and Schoonjans, {An Sofie} and Darina Prchalova and Marketa Havlovicova and Miroslava Hancarova and Magdalena Budisteanu and Annelies Dheedene and Bj{\"o}rn Menten and Dion, {Patrick A.} and Damien Lederer and Bert Callewaert",
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TY - JOUR

T1 - FOXP1-related intellectual disability syndrome

T2 - A recognisable entity

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 Angeles

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 J.L.

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

PY - 2017/9/1

Y1 - 2017/9/1

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.

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.

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U2 - 10.1136/jmedgenet-2017-104579

DO - 10.1136/jmedgenet-2017-104579

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VL - 54

SP - 613

EP - 623

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

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