Identification of 34 novel and 56 known FOXL2 mutations in patients with Blepharophimosis syndrome

Diane Beysen; Sarah De Jaegere; David Amor; Philippe Bouchard; Sophie Christin-Maitre; Marc Fellous; Philippe Touraine; Arthur W Grix; Raoul Hennekam; Françoise Meire; Nina Oyen; Louise C Wilson; Dalit Barel; Jill Clayton-Smith; Thomy de Ravel; Christian Decock; Patricia Delbeke; Regina Ensenauer; Friedrich Ebinger; Gabriele Gillessen-Kaesbach; Yvonne Hendriks; Virginia Kimonis; Rachel Laframboise; Paul Laissue; Kathleen Leppig; Bart P Leroy; David T Miller; David Mowat; Luitgard Neumann; Astrid Plomp; Nicole Van Regemorter; Dagmar Wieczorek; Reiner A Veitia; Anne De Paepe; Elfride De Baere

doi:10.1002/humu.20819

Identification of 34 novel and 56 known FOXL2 mutations in patients with Blepharophimosis syndrome

Diane Beysen, Sarah De Jaegere, David Amor, Philippe Bouchard, Sophie Christin-Maitre, Marc Fellous, Philippe Touraine, Arthur W Grix, Raoul Hennekam, Françoise Meire, Nina Oyen, Louise C Wilson, Dalit Barel, Jill Clayton-Smith, Thomy de Ravel, Christian Decock, Patricia Delbeke, Regina Ensenauer, Friedrich Ebinger, Gabriele Gillessen-KaesbachYvonne Hendriks, Virginia Kimonis, Rachel Laframboise, Paul Laissue, Kathleen Leppig, Bart P Leroy, David T Miller, David Mowat, Luitgard Neumann, Astrid Plomp, Nicole Van Regemorter, Dagmar Wieczorek, Reiner A Veitia, Anne De Paepe, Elfride De Baere

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Abstract

Blepharophimosis syndrome (BPES) is caused by loss-of-function mutations in the single-exon forkhead transcription factor gene FOXL2 and by genomic rearrangements of the FOXL2 locus. Here, we focus on 92 new intragenic FOXL2 mutations, 34 of which are novel. Specifically, we found 10 nonsense mutations (11%), 13 missense mutations (14%), 40 deletions or insertions leading to a frameshift (43%), and 29 in-frame changes (32%), of which 28 (30%) lead to a polyalanine expansion. This study confirms the existence of two previously described mutational hotspots. Moreover, we gained novel insights in genotype-phenotype correlations, emphasizing the need to interpret genotype-phenotype correlations individually and always in the context of further clinical observations.

Original language	English
Pages (from-to)	E205-19
Number of pages	15
Journal	Human Mutation
Volume	29
Issue number	11
DOIs	https://doi.org/10.1002/humu.20819
Publication status	Published - Nov 2008

Bibliographical note

Keywords

Adolescent
Adult
Amino Acid Sequence
Blepharophimosis/genetics
Child
Child, Preschool
Codon, Nonsense
DNA Mutational Analysis
Eyelids/abnormalities
Female
Forkhead Box Protein L2
Forkhead Transcription Factors/genetics
Frameshift Mutation
Genotype
Humans
Infant
Infant, Newborn
Male
Middle Aged
Molecular Sequence Data
Mutation, Missense
Pedigree
Phenotype
Primary Ovarian Insufficiency/genetics
Sequence Alignment
Young Adult

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Beysen, D., De Jaegere, S., Amor, D., Bouchard, P., Christin-Maitre, S., Fellous, M., Touraine, P., Grix, A. W., Hennekam, R., Meire, F., Oyen, N., Wilson, L. C., Barel, D., Clayton-Smith, J., de Ravel, T., Decock, C., Delbeke, P., Ensenauer, R., Ebinger, F., ... De Baere, E. (2008). Identification of 34 novel and 56 known FOXL2 mutations in patients with Blepharophimosis syndrome. Human Mutation, 29(11), E205-19. https://doi.org/10.1002/humu.20819

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title = "Identification of 34 novel and 56 known FOXL2 mutations in patients with Blepharophimosis syndrome",

abstract = "Blepharophimosis syndrome (BPES) is caused by loss-of-function mutations in the single-exon forkhead transcription factor gene FOXL2 and by genomic rearrangements of the FOXL2 locus. Here, we focus on 92 new intragenic FOXL2 mutations, 34 of which are novel. Specifically, we found 10 nonsense mutations (11%), 13 missense mutations (14%), 40 deletions or insertions leading to a frameshift (43%), and 29 in-frame changes (32%), of which 28 (30%) lead to a polyalanine expansion. This study confirms the existence of two previously described mutational hotspots. Moreover, we gained novel insights in genotype-phenotype correlations, emphasizing the need to interpret genotype-phenotype correlations individually and always in the context of further clinical observations.",

keywords = "Adolescent, Adult, Amino Acid Sequence, Blepharophimosis/genetics, Child, Child, Preschool, Codon, Nonsense, DNA Mutational Analysis, Eyelids/abnormalities, Female, Forkhead Box Protein L2, Forkhead Transcription Factors/genetics, Frameshift Mutation, Genotype, Humans, Infant, Infant, Newborn, Male, Middle Aged, Molecular Sequence Data, Mutation, Missense, Pedigree, Phenotype, Primary Ovarian Insufficiency/genetics, Sequence Alignment, Young Adult",

author = "Diane Beysen and {De Jaegere}, Sarah and David Amor and Philippe Bouchard and Sophie Christin-Maitre and Marc Fellous and Philippe Touraine and Grix, {Arthur W} and Raoul Hennekam and Fran{\c c}oise Meire and Nina Oyen and Wilson, {Louise C} and Dalit Barel and Jill Clayton-Smith and {de Ravel}, Thomy and Christian Decock and Patricia Delbeke and Regina Ensenauer and Friedrich Ebinger and Gabriele Gillessen-Kaesbach and Yvonne Hendriks and Virginia Kimonis and Rachel Laframboise and Paul Laissue and Kathleen Leppig and Leroy, {Bart P} and Miller, {David T} and David Mowat and Luitgard Neumann and Astrid Plomp and {Van Regemorter}, Nicole and Dagmar Wieczorek and Veitia, {Reiner A} and {De Paepe}, Anne and {De Baere}, Elfride",

year = "2008",

month = nov,

doi = "10.1002/humu.20819",

language = "English",

volume = "29",

pages = "E205--19",

journal = "Human Mutation",

issn = "1059-7794",

publisher = "Wiley-Liss Inc.",

number = "11",

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Beysen, D, De Jaegere, S, Amor, D, Bouchard, P, Christin-Maitre, S, Fellous, M, Touraine, P, Grix, AW, Hennekam, R, Meire, F, Oyen, N, Wilson, LC, Barel, D, Clayton-Smith, J, de Ravel, T, Decock, C, Delbeke, P, Ensenauer, R, Ebinger, F, Gillessen-Kaesbach, G, Hendriks, Y, Kimonis, V, Laframboise, R, Laissue, P, Leppig, K, Leroy, BP, Miller, DT, Mowat, D, Neumann, L, Plomp, A, Van Regemorter, N, Wieczorek, D, Veitia, RA, De Paepe, A & De Baere, E 2008, 'Identification of 34 novel and 56 known FOXL2 mutations in patients with Blepharophimosis syndrome', Human Mutation, vol. 29, no. 11, pp. E205-19. https://doi.org/10.1002/humu.20819

TY - JOUR

T1 - Identification of 34 novel and 56 known FOXL2 mutations in patients with Blepharophimosis syndrome

AU - Beysen, Diane

AU - De Jaegere, Sarah

AU - Amor, David

AU - Bouchard, Philippe

AU - Christin-Maitre, Sophie

AU - Fellous, Marc

AU - Touraine, Philippe

AU - Grix, Arthur W

AU - Hennekam, Raoul

AU - Meire, Françoise

AU - Oyen, Nina

AU - Wilson, Louise C

AU - Barel, Dalit

AU - Clayton-Smith, Jill

AU - de Ravel, Thomy

AU - Decock, Christian

AU - Delbeke, Patricia

AU - Ensenauer, Regina

AU - Ebinger, Friedrich

AU - Gillessen-Kaesbach, Gabriele

AU - Hendriks, Yvonne

AU - Kimonis, Virginia

AU - Laframboise, Rachel

AU - Laissue, Paul

AU - Leppig, Kathleen

AU - Leroy, Bart P

AU - Miller, David T

AU - Mowat, David

AU - Neumann, Luitgard

AU - Plomp, Astrid

AU - Van Regemorter, Nicole

AU - Wieczorek, Dagmar

AU - Veitia, Reiner A

AU - De Paepe, Anne

AU - De Baere, Elfride

PY - 2008/11

Y1 - 2008/11

N2 - Blepharophimosis syndrome (BPES) is caused by loss-of-function mutations in the single-exon forkhead transcription factor gene FOXL2 and by genomic rearrangements of the FOXL2 locus. Here, we focus on 92 new intragenic FOXL2 mutations, 34 of which are novel. Specifically, we found 10 nonsense mutations (11%), 13 missense mutations (14%), 40 deletions or insertions leading to a frameshift (43%), and 29 in-frame changes (32%), of which 28 (30%) lead to a polyalanine expansion. This study confirms the existence of two previously described mutational hotspots. Moreover, we gained novel insights in genotype-phenotype correlations, emphasizing the need to interpret genotype-phenotype correlations individually and always in the context of further clinical observations.

AB - Blepharophimosis syndrome (BPES) is caused by loss-of-function mutations in the single-exon forkhead transcription factor gene FOXL2 and by genomic rearrangements of the FOXL2 locus. Here, we focus on 92 new intragenic FOXL2 mutations, 34 of which are novel. Specifically, we found 10 nonsense mutations (11%), 13 missense mutations (14%), 40 deletions or insertions leading to a frameshift (43%), and 29 in-frame changes (32%), of which 28 (30%) lead to a polyalanine expansion. This study confirms the existence of two previously described mutational hotspots. Moreover, we gained novel insights in genotype-phenotype correlations, emphasizing the need to interpret genotype-phenotype correlations individually and always in the context of further clinical observations.

KW - Adolescent

KW - Adult

KW - Amino Acid Sequence

KW - Blepharophimosis/genetics

KW - Child

KW - Child, Preschool

KW - Codon, Nonsense

KW - DNA Mutational Analysis

KW - Eyelids/abnormalities

KW - Female

KW - Forkhead Box Protein L2

KW - Forkhead Transcription Factors/genetics

KW - Frameshift Mutation

KW - Genotype

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Male

KW - Middle Aged

KW - Molecular Sequence Data

KW - Mutation, Missense

KW - Pedigree

KW - Phenotype

KW - Primary Ovarian Insufficiency/genetics

KW - Sequence Alignment

KW - Young Adult

U2 - 10.1002/humu.20819

DO - 10.1002/humu.20819

M3 - Article

C2 - 18642388

SN - 1059-7794

VL - 29

SP - E205-19

JO - Human Mutation

JF - Human Mutation

IS - 11

ER -

Identification of 34 novel and 56 known FOXL2 mutations in patients with Blepharophimosis syndrome

Abstract

Bibliographical note

Keywords

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