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Expanding the phenotype spectrum associated with pathogenic variants in the COL2A1 and COL11A1 genes.
Ann Hum Genet. 2020 09; 84(5):380-392.AH

Abstract

We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in the COL2A1 or COL11A1 genes. Using Sanger and next-generation sequencing, 11 different COL2A1 variants (seven novel), were identified in 13 families (19 affected individuals), all diagnosed with Stickler syndrome (STL) type 1. In nine families, the COL2A1 disease-causing variant arose de novo. Phenotypically, we observed myopia (95%) and retinal detachment (47%), joint hyperflexibility (92%), midface retrusion (84%), cleft palate (53%), and various degrees of hearing impairment (50%). One patient had a splenic artery aneurysm. One affected individual carrying pathogenic variant in COL2A1 showed no ocular signs including no evidence of membranous vitreous anomaly. In three families (seven affected individuals), three novel COL11A1 variants were found. The propositus with a de novo variant showed an ultrarare Marshall/STL overlap. In the second family, the only common clinical sign was postlingual progressive sensorineural hearing impairment (DFNA37). Affected individuals from the third family had typical STL2 signs. The spectrum of disease phenotypes associated with COL2A1 or COL11A1 variants continues to expand and includes typical STL and various bone dysplasias, but also nonsyndromic hearing impairment, isolated myopia with or without retinal detachment, and STL phenotype without clinically detectable ocular pathology.

Authors+Show Affiliations

Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.Department of Ophthalmology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.Reprofit International, Brno, Czech Republic.Department of Medical Genetics, Nemocnice České Budějovice, České Budějovice, Czech Republic.GENNET, Liberec, Czech Republic.Molecular Biology, AGEL Laboratories, Nový Jičín, Czech Republic.Molecular Biology, AGEL Laboratories, Nový Jičín, Czech Republic.DNA Laboratory, Department of Child Neurology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.Research Unit for Rare Diseases, Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.

Pub Type(s)

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

Language

eng

PubMed ID

32427345

Citation

Čopíková, Jana, et al. "Expanding the Phenotype Spectrum Associated With Pathogenic Variants in the COL2A1 and COL11A1 Genes." Annals of Human Genetics, vol. 84, no. 5, 2020, pp. 380-392.
Čopíková J, Paděrová J, Románková V, et al. Expanding the phenotype spectrum associated with pathogenic variants in the COL2A1 and COL11A1 genes. Ann Hum Genet. 2020;84(5):380-392.
Čopíková, J., Paděrová, J., Románková, V., Havlovicová, M., Balaščáková, M., Zelinová, M., Vejvalková, Š., Simandlová, M., Štěpánková, J., Hořínová, V., Kantorová, E., Křečková, G., Pospíšilová, J., Boday, A., Meszarosová, A. U., Turnovec, M., Votýpka, P., Lišková, P., & Kremlíková Pourová, R. (2020). Expanding the phenotype spectrum associated with pathogenic variants in the COL2A1 and COL11A1 genes. Annals of Human Genetics, 84(5), 380-392. https://doi.org/10.1111/ahg.12386
Čopíková J, et al. Expanding the Phenotype Spectrum Associated With Pathogenic Variants in the COL2A1 and COL11A1 Genes. Ann Hum Genet. 2020;84(5):380-392. PubMed PMID: 32427345.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expanding the phenotype spectrum associated with pathogenic variants in the COL2A1 and COL11A1 genes. AU - Čopíková,Jana, AU - Paděrová,Jana, AU - Románková,Věra, AU - Havlovicová,Markéta, AU - Balaščáková,Miroslava, AU - Zelinová,Michaela, AU - Vejvalková,Šárka, AU - Simandlová,Martina, AU - Štěpánková,Jana, AU - Hořínová,Věra, AU - Kantorová,Eva, AU - Křečková,Gabriela, AU - Pospíšilová,Jana, AU - Boday,Arpád, AU - Meszarosová,Anna Uhrová, AU - Turnovec,Marek, AU - Votýpka,Pavel, AU - Lišková,Petra, AU - Kremlíková Pourová,Radka, Y1 - 2020/05/19/ PY - 2019/12/31/received PY - 2020/03/30/revised PY - 2020/03/31/accepted PY - 2020/5/20/pubmed PY - 2021/3/25/medline PY - 2020/5/20/entrez KW - COL11A1 KW - COL2A1 KW - Marshall syndrome KW - Stickler syndrome KW - myopia KW - nonsyndromic hearing loss KW - retinal detachment SP - 380 EP - 392 JF - Annals of human genetics JO - Ann Hum Genet VL - 84 IS - 5 N2 - We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in the COL2A1 or COL11A1 genes. Using Sanger and next-generation sequencing, 11 different COL2A1 variants (seven novel), were identified in 13 families (19 affected individuals), all diagnosed with Stickler syndrome (STL) type 1. In nine families, the COL2A1 disease-causing variant arose de novo. Phenotypically, we observed myopia (95%) and retinal detachment (47%), joint hyperflexibility (92%), midface retrusion (84%), cleft palate (53%), and various degrees of hearing impairment (50%). One patient had a splenic artery aneurysm. One affected individual carrying pathogenic variant in COL2A1 showed no ocular signs including no evidence of membranous vitreous anomaly. In three families (seven affected individuals), three novel COL11A1 variants were found. The propositus with a de novo variant showed an ultrarare Marshall/STL overlap. In the second family, the only common clinical sign was postlingual progressive sensorineural hearing impairment (DFNA37). Affected individuals from the third family had typical STL2 signs. The spectrum of disease phenotypes associated with COL2A1 or COL11A1 variants continues to expand and includes typical STL and various bone dysplasias, but also nonsyndromic hearing impairment, isolated myopia with or without retinal detachment, and STL phenotype without clinically detectable ocular pathology. SN - 1469-1809 UR - https://www.unboundmedicine.com/medline/citation/32427345/Expanding_the_phenotype_spectrum_associated_with_pathogenic_variants_in_the_COL2A1_and_COL11A1_genes_ L2 - https://doi.org/10.1111/ahg.12386 DB - PRIME DP - Unbound Medicine ER -