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Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients.
Eur J Hum Genet. 2010 Aug; 18(8):872-80.EJ

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 (P<0.01). Overall, 20 of 23 sporadic patients with a COL2A1 mutation had either a cleft palate or retinal detachment with vitreous anomalies. The presence of vitreous anomalies, retinal tears or detachments, cleft palate and a positive family history were shown to be good indicators for a COL2A1 defect. In conclusion, we confirm that Stickler syndrome type 1 is predominantly caused by loss-of-function mutations in the COL2A1 gene as >90% 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.

Authors+Show Affiliations

Center for Medical Genetics, Ghent University Hospital, Gent, Belgium. [corrected]No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20179744

Citation

Hoornaert, Kristien P., et al. "Stickler Syndrome Caused By COL2A1 Mutations: Genotype-phenotype Correlation in a Series of 100 Patients." European Journal of Human Genetics : EJHG, vol. 18, no. 8, 2010, pp. 872-80.
Hoornaert KP, Vereecke I, Dewinter C, et al. Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients. Eur J Hum Genet. 2010;18(8):872-80.
Hoornaert, K. P., Vereecke, I., Dewinter, C., Rosenberg, T., Beemer, F. A., Leroy, J. G., Bendix, L., Björck, E., Bonduelle, M., Boute, O., Cormier-Daire, V., De Die-Smulders, C., Dieux-Coeslier, A., Dollfus, H., Elting, M., Green, A., Guerci, V. I., Hennekam, R. C., 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 : EJHG, 18(8), 872-80. https://doi.org/10.1038/ejhg.2010.23
Hoornaert KP, et al. Stickler Syndrome Caused By COL2A1 Mutations: Genotype-phenotype Correlation in a Series of 100 Patients. Eur J Hum Genet. 2010;18(8):872-80. PubMed PMID: 20179744.
* Article titles in AMA citation format should be in sentence-case
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 - Björck,Erik, AU - Bonduelle,Maryse, AU - Boute,Odile, AU - Cormier-Daire,Valerie, AU - De Die-Smulders,Christine, AU - Dieux-Coeslier,Anne, AU - Dollfus,Hélène, AU - Elting,Mariet, 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,Michèle, AU - McEntagart,Meriel, AU - Mendicino,Angela, AU - Morton,Jenny, AU - Orazio,Gabrielli, AU - Paquis,Véronique, AU - Reish,Orit, AU - Simola,Kalle O J, AU - Smithson,Sarah F, AU - Temple,Karen I, 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, Y1 - 2010/02/24/ PY - 2010/2/25/entrez PY - 2010/2/25/pubmed PY - 2010/11/3/medline SP - 872 EP - 80 JF - European journal of human genetics : EJHG JO - Eur J Hum Genet VL - 18 IS - 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 (P<0.01). Overall, 20 of 23 sporadic patients with a COL2A1 mutation had either a cleft palate or retinal detachment with vitreous anomalies. The presence of vitreous anomalies, retinal tears or detachments, cleft palate and a positive family history were shown to be good indicators for a COL2A1 defect. In conclusion, we confirm that Stickler syndrome type 1 is predominantly caused by loss-of-function mutations in the COL2A1 gene as >90% 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. SN - 1476-5438 UR - https://www.unboundmedicine.com/medline/citation/20179744/Stickler_syndrome_caused_by_COL2A1_mutations:_genotype_phenotype_correlation_in_a_series_of_100_patients_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20179744/ DB - PRIME DP - Unbound Medicine ER -