Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients

Kristien P. Hoornaert; Inge Vereecke; Chantal Dewinter; Thomas Rosenberg; Frits A. Beemer; Jules G. Leroy; Laila Bendix; Erik Bjorck; Maryse Bonduelle; Odile Boute; Valerie Cormier-Daire; Christine Smulders - de Die; Anne Dieux-Coeslier; Helene Dollfus; Mariet W. Elting; Andrew Green; Veronica I. Guerci; Raoul C. M. Hennekam; Yvonne Hilhorts-Hofstee; Muriel Holder; Carel Hoyng; Kristi J. Jones; Dragana Josifova; Ilkka Kaitila; Suzanne Kjaergaard; Yolande H. Kroes; Kristina Lagerstedt; Melissa Lees; Martine LeMerrer; Cinzia Magnani; Carlo Marcelis; Loreto Martorell; Michele Mathieu; Meriel McEntagart; Angela Mendicino; Jenny Morton; Gabrielli Orazio; Veronique Paquis; Orit Reish; Kalle O. J. Simola; Sarah F. Smithson; I. Karen Temple; Elisabeth Van Aken; Yolande van Bever; Jenneke van den Ende; Johanna M. van Hagen; Leopoldo Zelante; Riina Zordania; Anne De Paepe; Bart P. Leroy; Marc De Buyzere; Paul J. Coucke; Geert R. Mortier

doi:10.1038/ejhg.2010.23

Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients

Kristien P. Hoornaert, Inge Vereecke, Chantal Dewinter, Thomas Rosenberg, Frits A. Beemer, Jules G. Leroy, Laila Bendix, Erik Bjorck, Maryse Bonduelle, Odile Boute, Valerie Cormier-Daire, Christine Smulders - de Die, Anne Dieux-Coeslier, Helene Dollfus, Mariet W. Elting, Andrew Green, Veronica I. Guerci, Raoul C. M. Hennekam, Yvonne Hilhorts-Hofstee, Muriel HolderCarel Hoyng, Kristi J. Jones, Dragana Josifova, Ilkka Kaitila, Suzanne Kjaergaard, Yolande H. Kroes, Kristina Lagerstedt, Melissa Lees, Martine LeMerrer, Cinzia Magnani, Carlo Marcelis, Loreto Martorell, Michele Mathieu, Meriel McEntagart, Angela Mendicino, Jenny Morton, Gabrielli Orazio, Veronique Paquis, Orit Reish, Kalle O. J. Simola, Sarah F. Smithson, I. Karen Temple, Elisabeth Van Aken, Yolande van Bever, Jenneke van den Ende, Johanna M. van Hagen, Leopoldo Zelante, Riina Zordania, Anne De Paepe, Bart P. Leroy, Marc De Buyzere, Paul J. Coucke, Geert R. Mortier^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Stickler syndrome is an autosomal dominant connective tissue disorder caused by mutations in different collagen genes. The aim of our study was to define more precisely the phenotype and genotype of Stickler syndrome type 1 by investigating a large series of patients with a heterozygous mutation in COL2A1. In 188 probands with the clinical diagnosis of Stickler syndrome, the COL2A1 gene was analyzed by either a mutation scanning technique or bidirectional fluorescent DNA sequencing. The effect of splice site alterations was investigated by analyzing mRNA. Multiplex ligation-dependent amplification analysis was used for the detection of intragenic deletions. We identified 77 different COL2A1 mutations in 100 affected individuals. Analysis of the splice site mutations showed unusual RNA isoforms, most of which contained a premature stop codon. Vitreous anomalies and retinal detachments were found more frequently in patients with a COL2A1 mutation compared with the mutation-negative group (P90% of the mutations were predicted to result in nonsense-mediated decay. On the basis of binary regression analysis, we developed a scoring system that may be useful when evaluating patients with Stickler syndrome. European Journal of Human Genetics (2010) 18, 872-880; doi:10.1038/ejhg.2010.23; published online 24 February 2010

Original language	English
Pages (from-to)	872-880
Journal	European Journal of Human Genetics
Volume	18
Issue number	8
DOIs	https://doi.org/10.1038/ejhg.2010.23
Publication status	Published - Aug 2010

Keywords

COL2A1
Stickler syndrome
genotype-phenotype correlation
type II collagenopathies
splice site mutation

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10.1038/ejhg.2010.23

https://europepmc.org/articles/pmc2987380?pdf=renderLicence: Other

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Hoornaert, K. P., Vereecke, I., Dewinter, C., Rosenberg, T., Beemer, F. A., Leroy, J. G., Bendix, L., Bjorck, E., Bonduelle, M., Boute, O., Cormier-Daire, V., Smulders - de Die, C., Dieux-Coeslier, A., Dollfus, H., Elting, M. W., Green, A., Guerci, V. I., Hennekam, R. C. M., Hilhorts-Hofstee, Y., ... Mortier, G. R. (2010). Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients. European Journal of Human Genetics, 18(8), 872-880. https://doi.org/10.1038/ejhg.2010.23

@article{56bf6126e9b14347a25eb867117d27cb,

title = "Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients",

abstract = "Stickler syndrome is an autosomal dominant connective tissue disorder caused by mutations in different collagen genes. The aim of our study was to define more precisely the phenotype and genotype of Stickler syndrome type 1 by investigating a large series of patients with a heterozygous mutation in COL2A1. In 188 probands with the clinical diagnosis of Stickler syndrome, the COL2A1 gene was analyzed by either a mutation scanning technique or bidirectional fluorescent DNA sequencing. The effect of splice site alterations was investigated by analyzing mRNA. Multiplex ligation-dependent amplification analysis was used for the detection of intragenic deletions. We identified 77 different COL2A1 mutations in 100 affected individuals. Analysis of the splice site mutations showed unusual RNA isoforms, most of which contained a premature stop codon. Vitreous anomalies and retinal detachments were found more frequently in patients with a COL2A1 mutation compared with the mutation-negative group (P90\% of the mutations were predicted to result in nonsense-mediated decay. On the basis of binary regression analysis, we developed a scoring system that may be useful when evaluating patients with Stickler syndrome. European Journal of Human Genetics (2010) 18, 872-880; doi:10.1038/ejhg.2010.23; published online 24 February 2010",

keywords = "COL2A1, Stickler syndrome, genotype-phenotype correlation, type II collagenopathies, splice site mutation",

author = "Hoornaert, \{Kristien P.\} and Inge Vereecke and Chantal Dewinter and Thomas Rosenberg and Beemer, \{Frits A.\} and Leroy, \{Jules G.\} and Laila Bendix and Erik Bjorck and Maryse Bonduelle and Odile Boute and Valerie Cormier-Daire and \{Smulders - de Die\}, Christine and Anne Dieux-Coeslier and Helene Dollfus and Elting, \{Mariet W.\} and Andrew Green and Guerci, \{Veronica I.\} and Hennekam, \{Raoul C. M.\} and Yvonne Hilhorts-Hofstee and Muriel Holder and Carel Hoyng and Jones, \{Kristi J.\} and Dragana Josifova and Ilkka Kaitila and Suzanne Kjaergaard and Kroes, \{Yolande H.\} and Kristina Lagerstedt and Melissa Lees and Martine LeMerrer and Cinzia Magnani and Carlo Marcelis and Loreto Martorell and Michele Mathieu and Meriel McEntagart and Angela Mendicino and Jenny Morton and Gabrielli Orazio and Veronique Paquis and Orit Reish and Simola, \{Kalle O. J.\} and Smithson, \{Sarah F.\} and Temple, \{I. Karen\} and \{Van Aken\}, Elisabeth and \{van Bever\}, Yolande and \{van den Ende\}, Jenneke and \{van Hagen\}, \{Johanna M.\} and Leopoldo Zelante and Riina Zordania and \{De Paepe\}, Anne and Leroy, \{Bart P.\} and \{De Buyzere\}, Marc and Coucke, \{Paul J.\} and Mortier, \{Geert R.\}",

year = "2010",

month = aug,

doi = "10.1038/ejhg.2010.23",

language = "English",

volume = "18",

pages = "872--880",

journal = "European Journal of Human Genetics",

issn = "1018-4813",

publisher = "Springer",

number = "8",

}

Hoornaert, KP, Vereecke, I, Dewinter, C, Rosenberg, T, Beemer, FA, Leroy, JG, Bendix, L, Bjorck, E, Bonduelle, M, Boute, O, Cormier-Daire, V, Smulders - de Die, C, Dieux-Coeslier, A, Dollfus, H, Elting, MW, Green, A, Guerci, VI, Hennekam, RCM, Hilhorts-Hofstee, Y, Holder, M, Hoyng, C, Jones, KJ, Josifova, D, Kaitila, I, Kjaergaard, S, Kroes, YH, Lagerstedt, K, Lees, M, LeMerrer, M, Magnani, C, Marcelis, C, Martorell, L, Mathieu, M, McEntagart, M, Mendicino, A, Morton, J, Orazio, G, Paquis, V, Reish, O, Simola, KOJ, Smithson, SF, Temple, IK, Van Aken, E, van Bever, Y, van den Ende, J, van Hagen, JM, Zelante, L, Zordania, R, De Paepe, A, Leroy, BP, De Buyzere, M, Coucke, PJ & Mortier, GR 2010, 'Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients', European Journal of Human Genetics, vol. 18, no. 8, pp. 872-880. https://doi.org/10.1038/ejhg.2010.23

TY - JOUR

T1 - Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients

AU - Hoornaert, Kristien P.

AU - Vereecke, Inge

AU - Dewinter, Chantal

AU - Rosenberg, Thomas

AU - Beemer, Frits A.

AU - Leroy, Jules G.

AU - Bendix, Laila

AU - Bjorck, Erik

AU - Bonduelle, Maryse

AU - Boute, Odile

AU - Cormier-Daire, Valerie

AU - Smulders - de Die, Christine

AU - Dieux-Coeslier, Anne

AU - Dollfus, Helene

AU - Elting, Mariet W.

AU - Green, Andrew

AU - Guerci, Veronica I.

AU - Hennekam, Raoul C. M.

AU - Hilhorts-Hofstee, Yvonne

AU - Holder, Muriel

AU - Hoyng, Carel

AU - Jones, Kristi J.

AU - Josifova, Dragana

AU - Kaitila, Ilkka

AU - Kjaergaard, Suzanne

AU - Kroes, Yolande H.

AU - Lagerstedt, Kristina

AU - Lees, Melissa

AU - LeMerrer, Martine

AU - Magnani, Cinzia

AU - Marcelis, Carlo

AU - Martorell, Loreto

AU - Mathieu, Michele

AU - McEntagart, Meriel

AU - Mendicino, Angela

AU - Morton, Jenny

AU - Orazio, Gabrielli

AU - Paquis, Veronique

AU - Reish, Orit

AU - Simola, Kalle O. J.

AU - Smithson, Sarah F.

AU - Temple, I. Karen

AU - Van Aken, Elisabeth

AU - van Bever, Yolande

AU - van den Ende, Jenneke

AU - van Hagen, Johanna M.

AU - Zelante, Leopoldo

AU - Zordania, Riina

AU - De Paepe, Anne

AU - Leroy, Bart P.

AU - De Buyzere, Marc

AU - Coucke, Paul J.

AU - Mortier, Geert R.

PY - 2010/8

Y1 - 2010/8

N2 - Stickler syndrome is an autosomal dominant connective tissue disorder caused by mutations in different collagen genes. The aim of our study was to define more precisely the phenotype and genotype of Stickler syndrome type 1 by investigating a large series of patients with a heterozygous mutation in COL2A1. In 188 probands with the clinical diagnosis of Stickler syndrome, the COL2A1 gene was analyzed by either a mutation scanning technique or bidirectional fluorescent DNA sequencing. The effect of splice site alterations was investigated by analyzing mRNA. Multiplex ligation-dependent amplification analysis was used for the detection of intragenic deletions. We identified 77 different COL2A1 mutations in 100 affected individuals. Analysis of the splice site mutations showed unusual RNA isoforms, most of which contained a premature stop codon. Vitreous anomalies and retinal detachments were found more frequently in patients with a COL2A1 mutation compared with the mutation-negative group (P90% of the mutations were predicted to result in nonsense-mediated decay. On the basis of binary regression analysis, we developed a scoring system that may be useful when evaluating patients with Stickler syndrome. European Journal of Human Genetics (2010) 18, 872-880; doi:10.1038/ejhg.2010.23; published online 24 February 2010

AB - Stickler syndrome is an autosomal dominant connective tissue disorder caused by mutations in different collagen genes. The aim of our study was to define more precisely the phenotype and genotype of Stickler syndrome type 1 by investigating a large series of patients with a heterozygous mutation in COL2A1. In 188 probands with the clinical diagnosis of Stickler syndrome, the COL2A1 gene was analyzed by either a mutation scanning technique or bidirectional fluorescent DNA sequencing. The effect of splice site alterations was investigated by analyzing mRNA. Multiplex ligation-dependent amplification analysis was used for the detection of intragenic deletions. We identified 77 different COL2A1 mutations in 100 affected individuals. Analysis of the splice site mutations showed unusual RNA isoforms, most of which contained a premature stop codon. Vitreous anomalies and retinal detachments were found more frequently in patients with a COL2A1 mutation compared with the mutation-negative group (P90% of the mutations were predicted to result in nonsense-mediated decay. On the basis of binary regression analysis, we developed a scoring system that may be useful when evaluating patients with Stickler syndrome. European Journal of Human Genetics (2010) 18, 872-880; doi:10.1038/ejhg.2010.23; published online 24 February 2010

KW - COL2A1

KW - Stickler syndrome

KW - genotype-phenotype correlation

KW - type II collagenopathies

KW - splice site mutation

U2 - 10.1038/ejhg.2010.23

DO - 10.1038/ejhg.2010.23

M3 - Article

SN - 1018-4813

VL - 18

SP - 872

EP - 880

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 8

ER -

Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients

Abstract

Keywords

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