Expanding the phenotype spectrum associated with pathogenic variants in the COL2A1 and COL11A1 genes. 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. Annals of Human Genetics, May, 2020.
doi  abstract   bibtex   
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.
@article{copikova_expanding_2020,
	title = {Expanding the phenotype spectrum associated with pathogenic variants in the {COL2A1} and {COL11A1} genes},
	issn = {1469-1809},
	doi = {10.1111/ahg.12386},
	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.},
	language = {eng},
	journal = {Annals of Human Genetics},
	author = {Čopíková, Jana and Paděrová, Jana and Románková, Věra and Havlovicová, Markéta and Balaščáková, Miroslava and Zelinová, Michaela and Vejvalková, Šárka and Simandlová, Martina and Štěpánková, Jana and Hořínová, Věra and Kantorová, Eva and Křečková, Gabriela and Pospíšilová, Jana and Boday, Arpád and Meszarosová, Anna Uhrová and Turnovec, Marek and Votýpka, Pavel and Lišková, Petra and Kremlíková Pourová, Radka},
	month = may,
	year = {2020},
	pmid = {32427345},
	keywords = {COL11A1, COL2A1, Marshall syndrome, Stickler syndrome, myopia, nonsyndromic hearing loss, retinal detachment},
}
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