Publication

Exome sequencing identifies the first genetic determinants of sirenomelia in humans

Lecoquierre, F., Brehin, A-C., Coutant, S., Coursimault, J., Bazin, A., Finck, W., Benoist, G., Begorre, M., Beneteau, C., Cailliez, D., Chenal, P., De Jong, M., Degre, S., Devisme, L., Francannet, C., Gerard, B., Jeanne, C., Joubert, M., Journel, H., Laurichesse Delmas, H., Layet, V., Liquier, A., Mangione, R., Patrier, S., Pelluard, F., Petit, F., Tillouche, N., Van Ravenswaaij-Arts, C., Frebourg, T., Saugier-Veber, P., Gruchy, N., Nicolas, G. & Gerard, M., May-2020, In : Human Mutation. 41, 5, p. 926-933 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Lecoquierre, F., Brehin, A-C., Coutant, S., Coursimault, J., Bazin, A., Finck, W., Benoist, G., Begorre, M., Beneteau, C., Cailliez, D., Chenal, P., De Jong, M., Degre, S., Devisme, L., Francannet, C., Gerard, B., Jeanne, C., Joubert, M., Journel, H., ... Gerard, M. (2020). Exome sequencing identifies the first genetic determinants of sirenomelia in humans. Human Mutation, 41(5), 926-933. https://doi.org/10.1002/humu.23998

Author

Lecoquierre, Francois ; Brehin, Anne-Claire ; Coutant, Sophie ; Coursimault, Juliette ; Bazin, Anne ; Finck, Wilfrid ; Benoist, Guillaume ; Begorre, Marianne ; Beneteau, Claire ; Cailliez, Daniel ; Chenal, Pierre ; De Jong, Mirjam ; Degre, Sophie ; Devisme, Louise ; Francannet, Christine ; Gerard, Benedicte ; Jeanne, Corinne ; Joubert, Madeleine ; Journel, Hubert ; Laurichesse Delmas, Helene ; Layet, Valerie ; Liquier, Alain ; Mangione, Raphaele ; Patrier, Sophie ; Pelluard, Fanny ; Petit, Florence ; Tillouche, Nadia ; Van Ravenswaaij-Arts, Conny ; Frebourg, Thierry ; Saugier-Veber, Pascale ; Gruchy, Nicolas ; Nicolas, Gael ; Gerard, Marion. / Exome sequencing identifies the first genetic determinants of sirenomelia in humans. In: Human Mutation. 2020 ; Vol. 41, No. 5. pp. 926-933.

Harvard

Lecoquierre, F, Brehin, A-C, Coutant, S, Coursimault, J, Bazin, A, Finck, W, Benoist, G, Begorre, M, Beneteau, C, Cailliez, D, Chenal, P, De Jong, M, Degre, S, Devisme, L, Francannet, C, Gerard, B, Jeanne, C, Joubert, M, Journel, H, Laurichesse Delmas, H, Layet, V, Liquier, A, Mangione, R, Patrier, S, Pelluard, F, Petit, F, Tillouche, N, Van Ravenswaaij-Arts, C, Frebourg, T, Saugier-Veber, P, Gruchy, N, Nicolas, G & Gerard, M 2020, 'Exome sequencing identifies the first genetic determinants of sirenomelia in humans', Human Mutation, vol. 41, no. 5, pp. 926-933. https://doi.org/10.1002/humu.23998

Standard

Exome sequencing identifies the first genetic determinants of sirenomelia in humans. / Lecoquierre, Francois; Brehin, Anne-Claire; Coutant, Sophie; Coursimault, Juliette; Bazin, Anne; Finck, Wilfrid; Benoist, Guillaume; Begorre, Marianne; Beneteau, Claire; Cailliez, Daniel; Chenal, Pierre; De Jong, Mirjam; Degre, Sophie; Devisme, Louise; Francannet, Christine; Gerard, Benedicte; Jeanne, Corinne; Joubert, Madeleine; Journel, Hubert; Laurichesse Delmas, Helene; Layet, Valerie; Liquier, Alain; Mangione, Raphaele; Patrier, Sophie; Pelluard, Fanny; Petit, Florence; Tillouche, Nadia; Van Ravenswaaij-Arts, Conny; Frebourg, Thierry; Saugier-Veber, Pascale; Gruchy, Nicolas; Nicolas, Gael; Gerard, Marion.

In: Human Mutation, Vol. 41, No. 5, 05.2020, p. 926-933.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Lecoquierre F, Brehin A-C, Coutant S, Coursimault J, Bazin A, Finck W et al. Exome sequencing identifies the first genetic determinants of sirenomelia in humans. Human Mutation. 2020 May;41(5):926-933. https://doi.org/10.1002/humu.23998


BibTeX

@article{0ac3ca3a645840da92aeb9d82ef21217,
title = "Exome sequencing identifies the first genetic determinants of sirenomelia in humans",
abstract = "Sirenomelia is a rare severe malformation sequence of unknown cause characterized by fused legs and severe visceral abnormalities. We present a series of nine families including two rare familial aggregations of sirenomelia investigated by a trio-based exome sequencing strategy. This approach identified CDX2 variants in the two familial aggregations, both fitting an autosomal dominant pattern of inheritance with variable expressivity. CDX2 is a major regulator of caudal development in vertebrate and mouse heterozygotes are a previously described model of sirenomelia. Remarkably, the p.(Arg237His) variant has already been reported in a patient with persistent cloaca. Analysis of the sporadic cases revealed six additional candidate variants including a de novo frameshift variant in the genetically constrained NKD1 gene, encoding a known interactor of CDX2. We provide the first insights for a genetic contribution in human sirenomelia and highlight the role of Cdx and Wnt signaling pathways in the development of this disorder.",
keywords = "caudal dysgenesis, CDX2, de novo mutation, exome sequencing, Sirenomelia, CAUDAL REGRESSION, DEFECTS, REQUIREMENT, GROWTH",
author = "Francois Lecoquierre and Anne-Claire Brehin and Sophie Coutant and Juliette Coursimault and Anne Bazin and Wilfrid Finck and Guillaume Benoist and Marianne Begorre and Claire Beneteau and Daniel Cailliez and Pierre Chenal and {De Jong}, Mirjam and Sophie Degre and Louise Devisme and Christine Francannet and Benedicte Gerard and Corinne Jeanne and Madeleine Joubert and Hubert Journel and {Laurichesse Delmas}, Helene and Valerie Layet and Alain Liquier and Raphaele Mangione and Sophie Patrier and Fanny Pelluard and Florence Petit and Nadia Tillouche and {Van Ravenswaaij-Arts}, Conny and Thierry Frebourg and Pascale Saugier-Veber and Nicolas Gruchy and Gael Nicolas and Marion Gerard",
year = "2020",
month = may,
doi = "10.1002/humu.23998",
language = "English",
volume = "41",
pages = "926--933",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "Wiley",
number = "5",

}

RIS

TY - JOUR

T1 - Exome sequencing identifies the first genetic determinants of sirenomelia in humans

AU - Lecoquierre, Francois

AU - Brehin, Anne-Claire

AU - Coutant, Sophie

AU - Coursimault, Juliette

AU - Bazin, Anne

AU - Finck, Wilfrid

AU - Benoist, Guillaume

AU - Begorre, Marianne

AU - Beneteau, Claire

AU - Cailliez, Daniel

AU - Chenal, Pierre

AU - De Jong, Mirjam

AU - Degre, Sophie

AU - Devisme, Louise

AU - Francannet, Christine

AU - Gerard, Benedicte

AU - Jeanne, Corinne

AU - Joubert, Madeleine

AU - Journel, Hubert

AU - Laurichesse Delmas, Helene

AU - Layet, Valerie

AU - Liquier, Alain

AU - Mangione, Raphaele

AU - Patrier, Sophie

AU - Pelluard, Fanny

AU - Petit, Florence

AU - Tillouche, Nadia

AU - Van Ravenswaaij-Arts, Conny

AU - Frebourg, Thierry

AU - Saugier-Veber, Pascale

AU - Gruchy, Nicolas

AU - Nicolas, Gael

AU - Gerard, Marion

PY - 2020/5

Y1 - 2020/5

N2 - Sirenomelia is a rare severe malformation sequence of unknown cause characterized by fused legs and severe visceral abnormalities. We present a series of nine families including two rare familial aggregations of sirenomelia investigated by a trio-based exome sequencing strategy. This approach identified CDX2 variants in the two familial aggregations, both fitting an autosomal dominant pattern of inheritance with variable expressivity. CDX2 is a major regulator of caudal development in vertebrate and mouse heterozygotes are a previously described model of sirenomelia. Remarkably, the p.(Arg237His) variant has already been reported in a patient with persistent cloaca. Analysis of the sporadic cases revealed six additional candidate variants including a de novo frameshift variant in the genetically constrained NKD1 gene, encoding a known interactor of CDX2. We provide the first insights for a genetic contribution in human sirenomelia and highlight the role of Cdx and Wnt signaling pathways in the development of this disorder.

AB - Sirenomelia is a rare severe malformation sequence of unknown cause characterized by fused legs and severe visceral abnormalities. We present a series of nine families including two rare familial aggregations of sirenomelia investigated by a trio-based exome sequencing strategy. This approach identified CDX2 variants in the two familial aggregations, both fitting an autosomal dominant pattern of inheritance with variable expressivity. CDX2 is a major regulator of caudal development in vertebrate and mouse heterozygotes are a previously described model of sirenomelia. Remarkably, the p.(Arg237His) variant has already been reported in a patient with persistent cloaca. Analysis of the sporadic cases revealed six additional candidate variants including a de novo frameshift variant in the genetically constrained NKD1 gene, encoding a known interactor of CDX2. We provide the first insights for a genetic contribution in human sirenomelia and highlight the role of Cdx and Wnt signaling pathways in the development of this disorder.

KW - caudal dysgenesis

KW - CDX2

KW - de novo mutation

KW - exome sequencing

KW - Sirenomelia

KW - CAUDAL REGRESSION

KW - DEFECTS

KW - REQUIREMENT

KW - GROWTH

U2 - 10.1002/humu.23998

DO - 10.1002/humu.23998

M3 - Article

VL - 41

SP - 926

EP - 933

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 5

ER -

ID: 133421242