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

  title={Expanding the phenotype spectrum associated with pathogenic variants in the COL2A1 and COL11A1 genes},
  author={Jana {\vC}op{\'i}kov{\'a} and Jana Paděrov{\'a} and Věra Rom{\'a}nkov{\'a} and Mark{\'e}ta Havlovicov{\'a} and Miroslava Bala{\vs}{\vc}{\'a}kov{\'a} and Michaela Zelinov{\'a} and {\vS}{\'a}rka Vejvalkov{\'a} and Martina Simandlov{\'a} and Jana {\vS}těp{\'a}nkov{\'a} and Věra Hoř{\'i}nov{\'a} and Eva Kantorov{\'a} and Gabriela Kře{\vc}kov{\'a} and Jana Posp{\'i}{\vs}ilov{\'a} and Arp{\'a}d Boday and Anna Uhrov{\'a} M{\'e}sz{\'a}rosov{\'a} and Marek Turnovec and Pavel Vot{\'y}pka and Petra Li{\vs}kov{\'a} and Radka Kreml{\'i}kov{\'a} Pourov{\'a}},
  journal={Annals of Human Genetics},
  pages={380 - 392}
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… 
3 Citations
Aberrant COL11A1 splicing causes prelingual autosomal dominant nonsyndromic hearing loss in the DFNA37 locus
Clinical and molecular genetic evidence is provided to unambiguously confirm that COL11A1 splice‐altering variants cause DFNA37 hearing loss and affirm that COL 11A1 be included in the genetic testing of patients with nonsyndromic deafness.
Genetic Characteristics and Phenotype of Korean Patients with Stickler Syndrome: A Korean Multicenter Analysis Report No. 1
  • Soon-Il Choi, Se-Joon Woo, +8 authors Sang-Jin Kim
  • Medicine
  • 2021
This is the first large-scale study of Koreans with Stickler syndrome, which will expand the spectrum of genetic variations of Stickler syndromes to include novel variants and missense variants.
Stickler Syndrome: A Review of Clinical Manifestations and the Genetics Evaluation
Molecular genetic testing should be considered in all individuals with suspected SS, as diagnosis not only assists in treatment and management of the patient but may also help identify other at-risk family members.


Mutation Update for COL2A1 Gene Variants Associated with Type II Collagenopathies
A review of COL2A1 mutations extracted from the Leiden Open Variation Database (LOVD) that was updated with data from PubMed and patients to provide support and potential collaborative material for scientific and clinical projects aimed at elucidating phenotype–genotype correlation and differential diagnosis in patients with type II collagenopathies.
Marshall syndrome: Further evidence of a distinct phenotypic entity and report of new findings
Detailed phenotypic and genetic description of dominant and recessive forms of Marshall syndrome due to COL11A1 mutations are depicted.
Splice-altering variant in COL11A1 as a cause of nonsyndromic hearing loss DFNA37
The COL11A1 gene is identified as the gene responsible for deafness at the DFNA37 locus, a novel canonical acceptor splice-site variant c.652-2A>C that is highly conserved, and confirmed in vitro to alter RNA splicing.
Stickler syndrome caused by COL2A1 mutations: genotype–phenotype correlation in a series of 100 patients
It is confirmed 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.
Fibrochondrogenesis results from mutations in the COL11A1 type XI collagen gene.
Findings identify COL11A1 as a locus for fibrochondrogenesis and indicate that there might be phenotypic manifestations among carriers, as well as noting early-onset hearing loss in both parents who carried a loss-of-function allele.
The phenotypic spectrum in patients with arginine to cysteine mutations in the COL2A1 gene
Arginine to cysteine mutations are rather infrequent COL2A1 mutations which cause a spectrum of phenotypes including classic SEDC and Stickler dysplasia, but also some unusual entities that have not yet been recognised and described as type II collagenopathies.
Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes.
Genotypic-phenotypic comparison revealed an association between the Marshall syndrome phenotype and splicing mutations of 54-bp exons in the C-terminal region of the COL11A1 gene, which led to a typical phenotype of Stickler syndrome.
Stickler syndrome and the vitreous phenotype: mutations in COL2A1 and COL11A1
It is now apparent that a new sub‐group of COL2A1 mutations is emerging that result in a different phenotype with a hypoplastic vitreous that fills the posterior chamber of the eye, and is either optically empty or has sparse irregular lamellae.
The Stickler syndrome: Genotype/phenotype correlation in 10 families with Stickler syndrome resulting from seven mutations in the type II collagen gene locus COL2A1
Although the molecular determination of a COL2A1 mutation can predict the occurrence of Stickler syndrome, the variability observed in the families described here makes it difficult to predict the severity of the phenotype on the basis of genotype.
A type II collagen mutation also results in oto-spondylo-megaepiphyseal dysplasia
These findings highlight the genetic heterogeneity of OSMED and extend the phenotypic spectrum of type II collagenopathy, as well as confirming the overlap between type II and type XI collagenopathies.