Expanding the phenotype spectrum associated with pathogenic variants in the COL2A1 and COL11A1 genes.

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. © 2020 John Wiley & Sons Ltd/University College London.

Citation

Jana Čopíková, Jana Paděrová, Věra Románková, Markéta Havlovicová, Miroslava Balaščáková, Michaela Zelinová, Šárka Vejvalková, Martina Simandlová, Jana Štěpánková, Věra Hořínová, Eva Kantorová, Gabriela Křečková, Jana Pospíšilová, Arpád Boday, Anna Uhrová Meszarosová, Marek Turnovec, Pavel Votýpka, Petra Lišková, Radka Kremlíková Pourová. Expanding the phenotype spectrum associated with pathogenic variants in the COL2A1 and COL11A1 genes. Annals of human genetics. 2020 Sep;84(5):380-392

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PMID: 32427345

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