Publication

Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome

Gordon, C. T., Vuillot, A., Marlin, S., Gerkes, E., Henderson, A., AlKindy, A., Holder-Espinasse, M., Park, S. S., Omarjee, A., Sanchis-Borja, M., Ben Bdira, E., Oufadem, M., Sikkema-Raddatz, B., Stewart, A., Palmer, R., McGowan, R., Petit, F., Delobel, B., Speicher, M. R., Aurora, P., Kilner, D., Pellerin, P., Simon, M., Bonnefont, J-P., Tobias, E. S., Garcia-Minaur, S., Bitner-Glindzicz, M., Lindholm, P., Meijer, B. A., Abadie, V., Denoyelle, F., Vazquez, M-P., Rotky-Fast, C., Couloigner, V., Pierrot, S., Manach, Y., Breton, S., Hendriks, Y. M. C., Munnich, A., Jakobsen, L., Kroisel, P., Lin, A., Kaban, L. B., Basel-Vanagaite, L., Wilson, L., Cunningham, M. L., Lyonnet, S. & Amiel, J., Mar-2013, In : JOURNAL OF MEDICAL GENETICS. 50, 3, p. 174-186 13 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Gordon, C. T., Vuillot, A., Marlin, S., Gerkes, E., Henderson, A., AlKindy, A., Holder-Espinasse, M., Park, S. S., Omarjee, A., Sanchis-Borja, M., Ben Bdira, E., Oufadem, M., Sikkema-Raddatz, B., Stewart, A., Palmer, R., McGowan, R., Petit, F., Delobel, B., Speicher, M. R., ... Amiel, J. (2013). Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome. JOURNAL OF MEDICAL GENETICS, 50(3), 174-186. https://doi.org/10.1136/jmedgenet-2012-101331

Author

Gordon, Christopher T. ; Vuillot, Alice ; Marlin, Sandrine ; Gerkes, Erica ; Henderson, Alex ; AlKindy, Adila ; Holder-Espinasse, Muriel ; Park, Sarah S. ; Omarjee, Asma ; Sanchis-Borja, Mateo ; Ben Bdira, Eya ; Oufadem, Myriam ; Sikkema-Raddatz, Birgit ; Stewart, Alison ; Palmer, Rodger ; McGowan, Ruth ; Petit, Florence ; Delobel, Bruno ; Speicher, Michael R. ; Aurora, Paul ; Kilner, David ; Pellerin, Philippe ; Simon, Marie ; Bonnefont, Jean-Paul ; Tobias, Edward S. ; Garcia-Minaur, Sixto ; Bitner-Glindzicz, Maria ; Lindholm, Pernille ; Meijer, Brigitte A. ; Abadie, Veronique ; Denoyelle, Francoise ; Vazquez, Marie-Paule ; Rotky-Fast, Christa ; Couloigner, Vincent ; Pierrot, Sebastien ; Manach, Yves ; Breton, Sylvain ; Hendriks, Yvonne M. C. ; Munnich, Arnold ; Jakobsen, Linda ; Kroisel, Peter ; Lin, Angela ; Kaban, Leonard B. ; Basel-Vanagaite, Lina ; Wilson, Louise ; Cunningham, Michael L. ; Lyonnet, Stanislas ; Amiel, Jeanne. / Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome. In: JOURNAL OF MEDICAL GENETICS. 2013 ; Vol. 50, No. 3. pp. 174-186.

Harvard

Gordon, CT, Vuillot, A, Marlin, S, Gerkes, E, Henderson, A, AlKindy, A, Holder-Espinasse, M, Park, SS, Omarjee, A, Sanchis-Borja, M, Ben Bdira, E, Oufadem, M, Sikkema-Raddatz, B, Stewart, A, Palmer, R, McGowan, R, Petit, F, Delobel, B, Speicher, MR, Aurora, P, Kilner, D, Pellerin, P, Simon, M, Bonnefont, J-P, Tobias, ES, Garcia-Minaur, S, Bitner-Glindzicz, M, Lindholm, P, Meijer, BA, Abadie, V, Denoyelle, F, Vazquez, M-P, Rotky-Fast, C, Couloigner, V, Pierrot, S, Manach, Y, Breton, S, Hendriks, YMC, Munnich, A, Jakobsen, L, Kroisel, P, Lin, A, Kaban, LB, Basel-Vanagaite, L, Wilson, L, Cunningham, ML, Lyonnet, S & Amiel, J 2013, 'Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome', JOURNAL OF MEDICAL GENETICS, vol. 50, no. 3, pp. 174-186. https://doi.org/10.1136/jmedgenet-2012-101331

Standard

Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome. / Gordon, Christopher T.; Vuillot, Alice; Marlin, Sandrine; Gerkes, Erica; Henderson, Alex; AlKindy, Adila; Holder-Espinasse, Muriel; Park, Sarah S.; Omarjee, Asma; Sanchis-Borja, Mateo; Ben Bdira, Eya; Oufadem, Myriam; Sikkema-Raddatz, Birgit; Stewart, Alison; Palmer, Rodger; McGowan, Ruth; Petit, Florence; Delobel, Bruno; Speicher, Michael R.; Aurora, Paul; Kilner, David; Pellerin, Philippe; Simon, Marie; Bonnefont, Jean-Paul; Tobias, Edward S.; Garcia-Minaur, Sixto; Bitner-Glindzicz, Maria; Lindholm, Pernille; Meijer, Brigitte A.; Abadie, Veronique; Denoyelle, Francoise; Vazquez, Marie-Paule; Rotky-Fast, Christa; Couloigner, Vincent; Pierrot, Sebastien; Manach, Yves; Breton, Sylvain; Hendriks, Yvonne M. C.; Munnich, Arnold; Jakobsen, Linda; Kroisel, Peter; Lin, Angela; Kaban, Leonard B.; Basel-Vanagaite, Lina; Wilson, Louise; Cunningham, Michael L.; Lyonnet, Stanislas; Amiel, Jeanne.

In: JOURNAL OF MEDICAL GENETICS, Vol. 50, No. 3, 03.2013, p. 174-186.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Gordon CT, Vuillot A, Marlin S, Gerkes E, Henderson A, AlKindy A et al. Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome. JOURNAL OF MEDICAL GENETICS. 2013 Mar;50(3):174-186. https://doi.org/10.1136/jmedgenet-2012-101331


BibTeX

@article{3eec2cebbc11491488e014eb6b904919,
title = "Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome",
abstract = "Background Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, beta 4 (PLCB4) and guanine nucleotide binding protein (G protein), a inhibiting activity polypeptide 3 (GNAI3) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development.Results We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients.Conclusions These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.",
keywords = "QUESTION MARK EAR, CONGENITAL AURICULAR CLEFT, PARKINSON-WHITE-SYNDROME, PROTEIN ALPHA-SUBUNITS, PHOSPHOLIPASE-C-BETA, CONDYLAR SYNDROME, ALAGILLE SYNDROME, DYSGNATHIA COMPLEX, DELETION, MICE",
author = "Gordon, {Christopher T.} and Alice Vuillot and Sandrine Marlin and Erica Gerkes and Alex Henderson and Adila AlKindy and Muriel Holder-Espinasse and Park, {Sarah S.} and Asma Omarjee and Mateo Sanchis-Borja and {Ben Bdira}, Eya and Myriam Oufadem and Birgit Sikkema-Raddatz and Alison Stewart and Rodger Palmer and Ruth McGowan and Florence Petit and Bruno Delobel and Speicher, {Michael R.} and Paul Aurora and David Kilner and Philippe Pellerin and Marie Simon and Jean-Paul Bonnefont and Tobias, {Edward S.} and Sixto Garcia-Minaur and Maria Bitner-Glindzicz and Pernille Lindholm and Meijer, {Brigitte A.} and Veronique Abadie and Francoise Denoyelle and Marie-Paule Vazquez and Christa Rotky-Fast and Vincent Couloigner and Sebastien Pierrot and Yves Manach and Sylvain Breton and Hendriks, {Yvonne M. C.} and Arnold Munnich and Linda Jakobsen and Peter Kroisel and Angela Lin and Kaban, {Leonard B.} and Lina Basel-Vanagaite and Louise Wilson and Cunningham, {Michael L.} and Stanislas Lyonnet and Jeanne Amiel",
year = "2013",
month = mar,
doi = "10.1136/jmedgenet-2012-101331",
language = "English",
volume = "50",
pages = "174--186",
journal = "JOURNAL OF MEDICAL GENETICS",
issn = "0022-2593",
publisher = "BMJ PUBLISHING GROUP",
number = "3",

}

RIS

TY - JOUR

T1 - Heterogeneity of mutational mechanisms and modes of inheritance in auriculocondylar syndrome

AU - Gordon, Christopher T.

AU - Vuillot, Alice

AU - Marlin, Sandrine

AU - Gerkes, Erica

AU - Henderson, Alex

AU - AlKindy, Adila

AU - Holder-Espinasse, Muriel

AU - Park, Sarah S.

AU - Omarjee, Asma

AU - Sanchis-Borja, Mateo

AU - Ben Bdira, Eya

AU - Oufadem, Myriam

AU - Sikkema-Raddatz, Birgit

AU - Stewart, Alison

AU - Palmer, Rodger

AU - McGowan, Ruth

AU - Petit, Florence

AU - Delobel, Bruno

AU - Speicher, Michael R.

AU - Aurora, Paul

AU - Kilner, David

AU - Pellerin, Philippe

AU - Simon, Marie

AU - Bonnefont, Jean-Paul

AU - Tobias, Edward S.

AU - Garcia-Minaur, Sixto

AU - Bitner-Glindzicz, Maria

AU - Lindholm, Pernille

AU - Meijer, Brigitte A.

AU - Abadie, Veronique

AU - Denoyelle, Francoise

AU - Vazquez, Marie-Paule

AU - Rotky-Fast, Christa

AU - Couloigner, Vincent

AU - Pierrot, Sebastien

AU - Manach, Yves

AU - Breton, Sylvain

AU - Hendriks, Yvonne M. C.

AU - Munnich, Arnold

AU - Jakobsen, Linda

AU - Kroisel, Peter

AU - Lin, Angela

AU - Kaban, Leonard B.

AU - Basel-Vanagaite, Lina

AU - Wilson, Louise

AU - Cunningham, Michael L.

AU - Lyonnet, Stanislas

AU - Amiel, Jeanne

PY - 2013/3

Y1 - 2013/3

N2 - Background Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, beta 4 (PLCB4) and guanine nucleotide binding protein (G protein), a inhibiting activity polypeptide 3 (GNAI3) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development.Results We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients.Conclusions These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.

AB - Background Auriculocondylar syndrome (ACS) is a rare craniofacial disorder consisting of micrognathia, mandibular condyle hypoplasia and a specific malformation of the ear at the junction between the lobe and helix. Missense heterozygous mutations in the phospholipase C, beta 4 (PLCB4) and guanine nucleotide binding protein (G protein), a inhibiting activity polypeptide 3 (GNAI3) genes have recently been identified in ACS patients by exome sequencing. These genes are predicted to function within the G protein-coupled endothelin receptor pathway during craniofacial development.Results We report eight additional cases ascribed to PLCB4 or GNAI3 gene lesions, comprising six heterozygous PLCB4 missense mutations, one heterozygous GNAI3 missense mutation and one homozygous PLCB4 intragenic deletion. Certain residues represent mutational hotspots; of the total of 11 ACS PLCB4 missense mutations now described, five disrupt Arg621 and two disrupt Asp360. The narrow distribution of mutations within protein space suggests that the mutations may result in dominantly interfering proteins, rather than haploinsufficiency. The consanguineous parents of the patient with a homozygous PLCB4 deletion each harboured the heterozygous deletion, but did not present the ACS phenotype, further suggesting that ACS is not caused by PLCB4 haploinsufficiency. In addition to ACS, the patient harbouring a homozygous deletion presented with central apnoea, a phenotype that has not been previously reported in ACS patients.Conclusions These findings indicate that ACS is not only genetically heterogeneous but also an autosomal dominant or recessive condition according to the nature of the PLCB4 gene lesion.

KW - QUESTION MARK EAR

KW - CONGENITAL AURICULAR CLEFT

KW - PARKINSON-WHITE-SYNDROME

KW - PROTEIN ALPHA-SUBUNITS

KW - PHOSPHOLIPASE-C-BETA

KW - CONDYLAR SYNDROME

KW - ALAGILLE SYNDROME

KW - DYSGNATHIA COMPLEX

KW - DELETION

KW - MICE

U2 - 10.1136/jmedgenet-2012-101331

DO - 10.1136/jmedgenet-2012-101331

M3 - Article

VL - 50

SP - 174

EP - 186

JO - JOURNAL OF MEDICAL GENETICS

JF - JOURNAL OF MEDICAL GENETICS

SN - 0022-2593

IS - 3

ER -

ID: 5788826