Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Pathophysiology Research Template

Target Disease

• Disease Name: Spondyloepimetaphyseal Dysplasia Strudwick Type
• MONDO ID: (if available)
• Category: Mendelian

Research Objectives

Please provide a comprehensive research report on the pathophysiology of Spondyloepimetaphyseal Dysplasia Strudwick Type. Focus on the molecular and cellular mechanisms underlying disease progression.

Required Information

1. Core Pathophysiology

• What are the primary pathophysiological mechanisms?
• What molecular pathways are dysregulated?
• What cellular processes are affected?

2. Key Molecular Players

• Genes/Proteins: Which genes are causally involved or implicated?
• Chemical Entities: What metabolites, drugs, or small molecules are relevant?
• Cell Types: Which cell types are primarily affected?
• Anatomical Locations: Which tissues/organs are involved?

3. Biological Processes (for GO annotation)

• What biological processes (GO terms) are disrupted?
• Consider: signaling pathways, metabolic processes, cellular responses, transport, etc.

4. Cellular Components

• Where in the cell do key processes occur?
• Consider: organelles, membrane compartments, extracellular space, etc.

5. Disease Progression

• What is the sequence of events from initial trigger to clinical manifestation?
• Are there distinct stages or phases?

6. Phenotypic Manifestations

• What are the key clinical phenotypes?
• How do they relate to the underlying mechanisms?

Citation Requirements

• Cite primary literature (PMID preferred) for all mechanistic claims
• Prioritize recent reviews and landmark papers
• Include direct quotes where possible to support key statements

Output Format

Structure your response as a narrative that could be used to populate a disease knowledge base entry with: - Pathophysiology description - Gene/protein annotations with ontology terms (HGNC, GO) - Phenotype associations (HP terms) - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Evidence items with PMIDs

Disease Pathophysiology Research Report: Spondyloepimetaphyseal Dysplasia, Strudwick Type (SEMD-ST)

Executive summary

Spondyloepimetaphyseal dysplasia, Strudwick type (SEMD-ST) is an autosomal dominant type II collagenopathy caused by pathogenic variants in COL2A1, the gene encoding the α1(II) chain of type II collagen, the major fibrillar collagen of hyaline cartilage. The dominant disease mechanism is typically dominant-negative disruption of procollagen-II folding/assembly (especially triple-helix glycine substitutions), resulting in defective cartilage extracellular matrix (ECM) and abnormal endochondral ossification. A central cellular pathology is impaired ER proteostasis in chondrocytes (ER retention/storage of mutant procollagen-II), which in some contexts activates ER stress/UPR and apoptosis, while recent 2024 human iPSC-derived cartilage models show that certain disease-causing COL2A1 substitutions can cause ER retention and matrix defects without a robust canonical unfolded protein response (UPR), implying variant-specific “failed surveillance” mechanisms that still culminate in defective ECM deposition. (aljuid2026col2a1mutationsand pages 7-8, aljuid2026col2a1mutationsand pages 8-9, yammine2023erprocollagenstorage pages 1-5, yammine2024humancartilagemodel pages 4-7)

1) Key concepts and definitions (current understanding)

1.1 Disease definition and identifiers

• Disease name: Spondyloepimetaphyseal dysplasia, Strudwick type (SEMD-ST).
• OMIM: 184250 (explicitly linked to SEMD Strudwick/type II collagenopathy and COL2A1 in comparative type II collagenopathy discussions). (machol2017cornerfracturetype pages 4-5)
• Inheritance: Autosomal dominant. (machol2017cornerfracturetype pages 4-5)
• MONDO / Orphanet: Not captured in the retrieved full-text evidence set; therefore not reported here.

1.2 How SEMD-ST fits within type II collagenopathies

• SEMD is described as essentially spondyloepiphyseal dysplasia (SED) with marked metaphyseal changes; metaphyseal abnormalities of long tubular bones become more evident with age. (morales2025theuseof pages 42-47)
• SEMD Strudwick is placed within the SEDC radiologic family (type II collagenopathy group) in radiology-focused classification: shared features include delayed ossification of juxtatruncal bones, vertebral abnormalities (e.g., pear-shaped vertebrae from characteristic contouring), and predominant short-trunk/short-neck short stature. (handa2021radiologicfeaturesof pages 2-3)

1.3 Core mechanistic concept: “Type II collagenopathy”

• Type II collagen (COL2A1 product) is a major structural component of hyaline cartilage ECM and is also relevant to vitreous and inner ear, consistent with extraskeletal ocular/auditory features observed across COL2A1 disorders. (nenna2019col2a1genemutations pages 2-3, handa2021radiologicfeaturesof pages 2-3)

2) Core pathophysiology (molecular and cellular mechanisms)

2.1 Primary molecular mechanisms

Mechanistically, COL2A1 disease can be conceptualized as two broad classes: 1. Dominant-negative structural variants (especially missense in the triple helix; glycine substitutions in the Gly-X-Y repeat) that produce abnormal procollagen-II that misfolds/assembles poorly and disrupts ECM. (nenna2019col2a1genemutations pages 2-3, aljuid2026col2a1mutationsand pages 7-8, morales2025theuseof pages 42-47) 2. Haploinsufficiency due to nonsense/frameshift/splice variants that trigger nonsense-mediated decay (NMD), lowering collagen II quantity and tending toward milder phenotypes within the COL2A1 spectrum. (nenna2019col2a1genemutations pages 2-3, aljuid2026col2a1mutationsand pages 7-8)

In SEMD-ST specifically, the molecular mechanism is generally described as dominant-negative COL2A1 mutations, often glycine substitutions. (morales2025theuseof pages 42-47)

2.2 Procollagen-II biosynthesis, folding, and ER proteostasis (central cellular hub)

A defining mechanistic hub is the endoplasmic reticulum (ER) of chondrocytes, where procollagen folds, undergoes post-translational modification, and is trafficked for secretion.

Recent 2024 mechanistic developments (human iPSC-derived cartilage models) - In a COL2A1 Gly1170Ser model, procollagen-II is slow to fold and secrete, accumulates intracellularly with an ER storage disorder phenotype, yet intracellular accumulation is not recognized by the UPR (uncoupled from canonical UPR activation). (yammine2023erprocollagenstorage pages 1-5) - Deeper mechanistic profiling in that model indicates mutant procollagen-II can become hypermodified, accumulate in a dilated ER, and still fail to mount a substantive UPR (e.g., BiP interaction not increased; RNA-seq lacking UPR activation), suggesting collagen triple-helix features may evade BiP-based sensing. (yammine2023erprocollagenstorage pages 15-18) - In a second 2024 iPSC-derived cartilage model (COL2A1 Arg719Cys), cartilage matrix is deposited but the collagen-II network is sparse/deficient and ER is distended, consistent with a storage defect; transcriptional matrisome changes are minimal, supporting a mechanism dominated by protein-level folding/assembly defects rather than broad gene-expression remodeling. (yammine2024humancartilagemodel pages 4-7, yammine2024humancartilagemodel pages 1-4) - That Arg719Cys model additionally supports a “failed surveillance” mechanism: the ER proteostasis network does not differentially engage the defective procollagen-II, implying defective collagen can evade quality-control recognition and still be secreted/accumulated, producing a defective ECM. (yammine2024humancartilagemodel pages 4-7, yammine2024humancartilagemodel pages 1-4)

Canonical (review-synthesized) ER stress/UPR-to-apoptosis model - In broader COL2A1/type II collagenopathy literature syntheses, intracellular retention of misfolded collagen can activate ER stress and UPR (PERK/ATF6/IRE1 branches), with downstream factors (ATF4, spliced XBP1) and if unresolved, induction of CHOP/caspases and chondrocyte apoptosis, disrupting growth-plate organization. (aljuid2026col2a1mutationsand pages 7-8, aljuid2026col2a1mutationsand pages 8-9)

Taken together, current understanding supports variant- and context-dependent ER stress biology: some COL2A1 variants may drive overt UPR/apoptosis, while others cause clinically meaningful ER storage and ECM insufficiency with minimal canonical UPR, implying additional non-canonical proteostasis failure modes. (yammine2023erprocollagenstorage pages 15-18, yammine2024humancartilagemodel pages 1-4)

2.3 ECM assembly defects and downstream tissue dysfunction

• Molecular/cellular defects in procollagen folding/secretion produce reduced extracellular collagen-II deposition and abnormal/sparse collagen fibrils, leading to defective cartilage mechanical properties and disrupted cartilage–bone coupling during endochondral ossification. (nenna2019col2a1genemutations pages 2-3, yammine2024humancartilagemodel pages 4-7)
• Growth plate architecture changes (including abnormal organization/proliferation in collagenopathy models) link molecular defects to impaired endochondral ossification and skeletal dysplasia phenotypes. (aljuid2026col2a1mutationsand pages 7-8, aljuid2026col2a1mutationsand pages 8-9)

3) Key molecular players

3.1 Genes/Proteins (causal and mechanistically implicated)

• COL2A1 (HGNC:2200): causal gene for SEMD-ST/type II collagenopathy. (machol2017cornerfracturetype pages 4-5, morales2025theuseof pages 42-47)
• ER stress/proteostasis signaling modules (mechanistic axis in collagenopathies): PERK/EIF2AK3, ATF6, IRE1/ERN1, XBP1, CHOP/DDIT3, and chaperone engagement (e.g., BiP/HSPA5 discussed as a key UPR sensor with limited differential engagement in specific collagen-II storage phenotypes). (aljuid2026col2a1mutationsand pages 7-8, yammine2023erprocollagenstorage pages 15-18)

3.2 Chemical entities / small molecules

• The most “relevant chemical entities” in the mechanistic evidence are amino acids defining pathogenic substitutions (e.g., glycine substitutions in Gly-X-Y and Arg→Cys substitutions), which are directly linked to folding and matrix phenotypes. (nenna2019col2a1genemutations pages 2-3, yammine2024humancartilagemodel pages 4-7)
• No disease-modifying drugs specific to SEMD-ST were identified in the retrieved mechanistic evidence set.

3.3 Cell types primarily affected

• Chondrocytes (cartilage-producing cells) are the central affected cell type because they synthesize procollagen-II and maintain cartilage ECM. (nenna2019col2a1genemutations pages 2-3, handa2021radiologicfeaturesof pages 2-3)
• Growth plate chondrocytes (conceptually) are implicated in abnormal endochondral ossification and short stature; growth-plate disorganization is a recurring downstream theme in collagenopathy models. (aljuid2026col2a1mutationsand pages 7-8, aljuid2026col2a1mutationsand pages 8-9)

3.4 Anatomical locations (tissues/organs)

• Hyaline cartilage (including growth plate and articular cartilage) is the primary tissue impacted. (nenna2019col2a1genemutations pages 2-3, handa2021radiologicfeaturesof pages 2-3)
• Spine/vertebral bodies: platyspondyly and related vertebral anomalies contribute to short trunk phenotype. (handa2021radiologicfeaturesof pages 2-3)
• Proximal femoral epiphysis/hip region: epiphyseal and hip deformities are common in COL2A1 dysplasia cohorts. (yeter2025diagnosticchallengeof pages 5-12)
• Cervical spine/odontoid process: odontoid hypoplasia and risk of atlanto-axial instability/spinal cord compression are emphasized. (morales2025theuseof pages 38-42, morales2025theuseof pages 42-47)
• Extraskeletal: eye (vitreous/retina) and inner ear, consistent with myopia/retinal detachment and hearing loss in COL2A1 disorders. (handa2021radiologicfeaturesof pages 2-3, terhal2015astudyof pages 3-4)

4) Biological processes disrupted (GO-oriented)

A practical GO-oriented set of disrupted processes supported by the evidence includes: - Collagen fibril organization / extracellular matrix organization (defective collagen-II network deposition, sparse fibrils). (nenna2019col2a1genemutations pages 2-3, yammine2024humancartilagemodel pages 4-7) - Protein folding and secretion (slow folding, slow secretion, hypermodification, ER retention). (yammine2023erprocollagenstorage pages 1-5, yammine2023erprocollagenstorage pages 15-18) - Endoplasmic reticulum stress / unfolded protein response (UPR) (context-dependent engagement; canonical PERK/ATF6/IRE1 axis in reviews; UPR uncoupling in 2024 iPSC models). (aljuid2026col2a1mutationsand pages 7-8, yammine2023erprocollagenstorage pages 15-18) - Chondrocyte differentiation / cartilage development / endochondral ossification (growth plate architectural disruption and skeletal dysplasia outcomes). (aljuid2026col2a1mutationsand pages 7-8, handa2021radiologicfeaturesof pages 2-3)

5) Cellular components involved

Key cellular locales (ontology-ready) are: - Rough endoplasmic reticulum (ER): site of procollagen folding and the location of ER storage/retention phenotypes with distended ER cisternae. (yammine2023erprocollagenstorage pages 1-5, yammine2024humancartilagemodel pages 1-4) - Extracellular matrix (collagen-containing ECM): defective collagen-II fibril networks and sparse matrices. (yammine2024humancartilagemodel pages 4-7)

6) Disease progression model (trigger → cellular pathology → clinical manifestation)

A synthesis consistent with the evidence: 1. Trigger: Heterozygous pathogenic COL2A1 variant (often triple-helix glycine substitution; sometimes other substitutions such as Arg→Cys). (nenna2019col2a1genemutations pages 2-3, yammine2024humancartilagemodel pages 4-7) 2. Early molecular effects: Slow folding/assembly of procollagen-II, excessive post-translational modification, reduced secretion, and partial intracellular retention (ER storage). (yammine2023erprocollagenstorage pages 1-5, yammine2023erprocollagenstorage pages 15-18, yammine2024humancartilagemodel pages 1-4) 3. Cellular stress and quality-control outcomes: - Some variants/models: ER retention elicits canonical ER stress/UPR signaling and can lead to apoptosis if unresolved. (aljuid2026col2a1mutationsand pages 7-8, aljuid2026col2a1mutationsand pages 8-9) - Other variants/models (2024): ER retention/storage and matrix failure can occur without robust UPR activation, suggesting “surveillance failure” in ER proteostasis. (yammine2023erprocollagenstorage pages 15-18, yammine2024humancartilagemodel pages 1-4) 4. Tissue-level effects: Deficient collagen-II ECM (sparse fibrils) compromises cartilage structure and growth plate organization, impairing endochondral ossification. (yammine2024humancartilagemodel pages 4-7, aljuid2026col2a1mutationsand pages 7-8) 5. Clinical evolution: Infancy resembles SEDC; with age, metaphyseal abnormalities become increasingly evident; spine/hip deformities and cervical instability risks become key management concerns. (morales2025theuseof pages 42-47, morales2025theuseof pages 38-42)

7) Phenotypic manifestations and mechanism links

7.1 Core skeletal phenotypes

• SEMD Strudwick is characterized as SED-like with marked metaphyseal abnormalities emerging with age. (morales2025theuseof pages 42-47)
• Radiologic family features include spine/pelvis/proximal epiphysis ossification delay and vertebral abnormalities contributing to short trunk/neck short stature. (handa2021radiologicfeaturesof pages 2-3)
• Cervical involvement: odontoid hypoplasia/non-fusion → risk of cervical instability and spinal cord compression. (morales2025theuseof pages 38-42, morales2025theuseof pages 42-47)

7.2 Extraskeletal phenotypes

• Ocular: vitreoretinal degeneration with severe myopia and retinal detachment occurs across type II collagenopathies; in a COL2A1 cohort, myopia and retinal detachment frequencies were quantified (see statistics below). (handa2021radiologicfeaturesof pages 2-3, terhal2015astudyof pages 3-4)
• Hearing: sensorineural/mixed hearing loss is part of the spectrum; quantified in cohort statistics below. (handa2021radiologicfeaturesof pages 2-3, terhal2015astudyof pages 3-4)

Mechanistic mapping: these reflect tissue distribution of type II collagen beyond growth plate cartilage. (handa2021radiologicfeaturesof pages 2-3)

8) Relevant statistics and data (cohorts; recent where available)

Although SEMD-ST itself is rare and often embedded within broader COL2A1 phenotype cohorts, multiple quantitative observations relevant to SEMD/ST biology are available.

8.1 COL2A1 cohort including SEMD cases (Terhal et al., 2015)

Study: “A study of the clinical and radiological features in a cohort of 93 patients with a COL2A1 mutation causing spondyloepiphyseal dysplasia congenita or a related phenotype” (publication date: March 2015; URL: https://doi.org/10.1002/ajmg.a.36922). (terhal2015astudyof pages 4-6) Key quantitative findings in the available excerpts: - 93 patients; median age 17 (range 4 months–70 years). (terhal2015astudyof pages 4-6) - Variant class: 68/93 (73%) had missense glycine substitutions in the triple helix. (terhal2015astudyof pages 4-6) - De novo variants: 47/93 (51%); inherited: 31/93 (33%). (terhal2015astudyof pages 4-6) - SEMD present in this broader cohort: SEMD (n = 5). (terhal2015astudyof pages 3-4) - Cervical spine: odontoid hypoplasia 56%; atlanto-axial instability in 5/18 (28%) among those with flexion–extension films. (terhal2015astudyof pages 3-4) - Ocular: myopia 45%; retinal detachment 12% (median age 14 years). (terhal2015astudyof pages 3-4) - Hearing loss: 37%. (terhal2015astudyof pages 3-4)

Terhal et al. also include multiple figures/tables (retrieved as cropped images) summarizing genotype groupings and phenotype correlations (e.g., ocular features and dens hypoplasia correlations). (terhal2015astudyof media 7e789bd0, terhal2015astudyof media 98be3c29)

8.2 Epidemiology statistic (from a concise review)

A concise clinical genetics review reports that spondyloepiphyseal dysplasia congenita (SEDC) is rare with an estimate of ~3.4/1,000,000 and describes frequent ocular/hearing involvement across COL2A1 disorders. (nenna2019col2a1genemutations pages 2-3)

9) Current applications and real-world implementations

9.1 Clinical implementation: surveillance and multidisciplinary care

Because SEMD-ST features include cervical spine risk (odontoid hypoplasia and instability) and frequent ocular/auditory complications across COL2A1 disorders, real-world management commonly includes orthopedic/spine monitoring and ophthalmology/audiology surveillance. Evidence of the prevalence of these complications in a large COL2A1 cohort supports this approach (e.g., quantified odontoid hypoplasia, retinal detachment, and hearing loss). (terhal2015astudyof pages 3-4)

9.2 Diagnostic implementation: phenotype-driven molecular testing

Radiology-driven pattern recognition is emphasized as a way to classify a case into the SEDC/type II collagenopathy family and direct targeted genetic testing (COL2A1). (handa2021radiologicfeaturesof pages 2-3)

9.3 Research implementation (2023–2024): human iPSC-derived cartilage disease models

A major recent development is the use of isogenic iPSC-derived chondrocytes/cartilage to model COL2A1 disease mechanisms in a human context. - These models enable high-resolution mechanistic studies (folding kinetics, proteostasis engagement, ER morphology) and can function as platforms for therapeutic strategy testing targeting ER proteostasis. (yammine2023erprocollagenstorage pages 1-5, yammine2023erprocollagenstorage pages 15-18)

10) Expert opinions / analysis (authoritative source perspectives)

• Radiology experts emphasize that accurate pattern recognition and family-based classification in collagenopathies is clinically actionable, because it guides appropriate genetic testing and informs anticipation of extraskeletal features (ocular/hearing). (handa2021radiologicfeaturesof pages 2-3)
• Mechanistic 2024 iPSC-derived cartilage studies provide an expert-driven reinterpretation of collagenopathy cell biology: ER retention of mutant procollagen-II may not necessarily trigger canonical UPR, reframing the assumption that ER storage equals UPR activation in all collagenopathies and highlighting “failed surveillance” as a plausible pathophysiologic theme. (yammine2023erprocollagenstorage pages 15-18, yammine2024humancartilagemodel pages 1-4)

Ontology-ready annotations (GO/CL/UBERON/HP/CHEBI-style)

The table below is structured to support direct knowledge-base ingestion.

Table: This table summarizes ontology-ready molecular, cellular, anatomical, and phenotypic annotations for COL2A1-related spondyloepimetaphyseal dysplasia Strudwick type. It highlights the main mechanistic axis from mutant collagen II proteostasis defects to extracellular matrix disorganization, growth-plate dysfunction, and characteristic skeletal and extraskeletal phenotypes.

Evidence items (PMIDs when available)

The retrieved full-text evidence provided DOIs/URLs and did not include PMIDs in the excerpts for most key items; therefore PMIDs are not reported here. Key evidence sources (with publication date and URL/DOI from the retrieved texts): - Terhal et al., 2015-03, Am J Med Genet A: https://doi.org/10.1002/ajmg.a.36922 (cohort statistics, includes SEMD n=5). (terhal2015astudyof pages 4-6, terhal2015astudyof pages 3-4) - Handa et al., 2021-01, RadioGraphics: https://doi.org/10.1148/rg.2021200075 (radiologic family classification; extraskeletal features). (handa2021radiologicfeaturesof pages 2-3) - Yammine et al., 2024-10 (BioRxiv), https://doi.org/10.1101/2023.10.19.562780 (Gly1170Ser ER storage uncoupled from UPR; proteostasis engagement; therapeutic implications). (yammine2023erprocollagenstorage pages 1-5, yammine2023erprocollagenstorage pages 15-18) - Yammine et al., 2024-11 (BioRxiv), https://doi.org/10.1101/2024.11.07.622468 (Arg719Cys matrix sparsity; ER distention; limited proteostasis recognition). (yammine2024humancartilagemodel pages 4-7, yammine2024humancartilagemodel pages 1-4) - Machol et al., 2017-11, Am J Med Genet A: https://doi.org/10.1002/ajmg.a.38059 (explicit OMIM 184250 linkage and AD inheritance context). (machol2017cornerfracturetype pages 4-5)

Limitations of this tool-based review

• MONDO/Orphanet identifiers and PMIDs were not present in the retrieved evidence snippets; thus they are not asserted here.
• 2023–2024 sources in the retrieved evidence set are primarily mechanistic preprints (BioRxiv) rather than final peer-reviewed publications; however, they directly address the requested molecular/cellular pathophysiology with high mechanistic resolution. (yammine2023erprocollagenstorage pages 1-5, yammine2024humancartilagemodel pages 1-4)

References

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13. (terhal2015astudyof pages 3-4): Paulien A. Terhal, Rutger Jan A. J. Nievelstein, Eva J. J. Verver, Vedat Topsakal, Paula van Dommelen, Kristien Hoornaert, Martine Le Merrer, Andreas Zankl, Marleen E. H. Simon, Sarah F. Smithson, Carlo Marcelis, Bronwyn Kerr, Jill Clayton‐Smith, Esther Kinning, Sahar Mansour, Frances Elmslie, Linda Goodwin, Annemarie H. van der Hout, Hermine E. Veenstra‐Knol, Johanna C. Herkert, Allan M. Lund, Raoul C. M. Hennekam, André Mégarbané, Melissa M. Lees, Louise C. Wilson, Alison Male, Jane Hurst, Yasemin Alanay, Göran Annerén, Regina C. Betz, Ernie M. H. F. Bongers, Valerie Cormier‐Daire, Anne Dieux, Albert David, Mariet W. Elting, Jenneke van den Ende, Andrew Green, Johanna M. van Hagen, Niels Thomas Hertel, Muriel Holder‐Espinasse, Nicolette den Hollander, Tessa Homfray, Hanne D. Hove, Susan Price, Annick Raas‐Rothschild, Marianne Rohrbach, Barbara Schroeter, Mohnish Suri, Elizabeth M. Thompson, Edward S. Tobias, Annick Toutain, Maaike Vreeburg, Emma Wakeling, Nine V. Knoers, Paul Coucke, and Geert R. Mortier. A study of the clinical and radiological features in a cohort of 93 patients with a col2a1 mutation causing spondyloepiphyseal dysplasia congenita or a related phenotype. American Journal of Medical Genetics Part A, 167:461-475, Mar 2015. URL: https://doi.org/10.1002/ajmg.a.36922, doi:10.1002/ajmg.a.36922. This article has 105 citations.

14. (terhal2015astudyof pages 4-6): Paulien A. Terhal, Rutger Jan A. J. Nievelstein, Eva J. J. Verver, Vedat Topsakal, Paula van Dommelen, Kristien Hoornaert, Martine Le Merrer, Andreas Zankl, Marleen E. H. Simon, Sarah F. Smithson, Carlo Marcelis, Bronwyn Kerr, Jill Clayton‐Smith, Esther Kinning, Sahar Mansour, Frances Elmslie, Linda Goodwin, Annemarie H. van der Hout, Hermine E. Veenstra‐Knol, Johanna C. Herkert, Allan M. Lund, Raoul C. M. Hennekam, André Mégarbané, Melissa M. Lees, Louise C. Wilson, Alison Male, Jane Hurst, Yasemin Alanay, Göran Annerén, Regina C. Betz, Ernie M. H. F. Bongers, Valerie Cormier‐Daire, Anne Dieux, Albert David, Mariet W. Elting, Jenneke van den Ende, Andrew Green, Johanna M. van Hagen, Niels Thomas Hertel, Muriel Holder‐Espinasse, Nicolette den Hollander, Tessa Homfray, Hanne D. Hove, Susan Price, Annick Raas‐Rothschild, Marianne Rohrbach, Barbara Schroeter, Mohnish Suri, Elizabeth M. Thompson, Edward S. Tobias, Annick Toutain, Maaike Vreeburg, Emma Wakeling, Nine V. Knoers, Paul Coucke, and Geert R. Mortier. A study of the clinical and radiological features in a cohort of 93 patients with a col2a1 mutation causing spondyloepiphyseal dysplasia congenita or a related phenotype. American Journal of Medical Genetics Part A, 167:461-475, Mar 2015. URL: https://doi.org/10.1002/ajmg.a.36922, doi:10.1002/ajmg.a.36922. This article has 105 citations.

15. (terhal2015astudyof media 7e789bd0): Paulien A. Terhal, Rutger Jan A. J. Nievelstein, Eva J. J. Verver, Vedat Topsakal, Paula van Dommelen, Kristien Hoornaert, Martine Le Merrer, Andreas Zankl, Marleen E. H. Simon, Sarah F. Smithson, Carlo Marcelis, Bronwyn Kerr, Jill Clayton‐Smith, Esther Kinning, Sahar Mansour, Frances Elmslie, Linda Goodwin, Annemarie H. van der Hout, Hermine E. Veenstra‐Knol, Johanna C. Herkert, Allan M. Lund, Raoul C. M. Hennekam, André Mégarbané, Melissa M. Lees, Louise C. Wilson, Alison Male, Jane Hurst, Yasemin Alanay, Göran Annerén, Regina C. Betz, Ernie M. H. F. Bongers, Valerie Cormier‐Daire, Anne Dieux, Albert David, Mariet W. Elting, Jenneke van den Ende, Andrew Green, Johanna M. van Hagen, Niels Thomas Hertel, Muriel Holder‐Espinasse, Nicolette den Hollander, Tessa Homfray, Hanne D. Hove, Susan Price, Annick Raas‐Rothschild, Marianne Rohrbach, Barbara Schroeter, Mohnish Suri, Elizabeth M. Thompson, Edward S. Tobias, Annick Toutain, Maaike Vreeburg, Emma Wakeling, Nine V. Knoers, Paul Coucke, and Geert R. Mortier. A study of the clinical and radiological features in a cohort of 93 patients with a col2a1 mutation causing spondyloepiphyseal dysplasia congenita or a related phenotype. American Journal of Medical Genetics Part A, 167:461-475, Mar 2015. URL: https://doi.org/10.1002/ajmg.a.36922, doi:10.1002/ajmg.a.36922. This article has 105 citations.

16. (terhal2015astudyof media 98be3c29): Paulien A. Terhal, Rutger Jan A. J. Nievelstein, Eva J. J. Verver, Vedat Topsakal, Paula van Dommelen, Kristien Hoornaert, Martine Le Merrer, Andreas Zankl, Marleen E. H. Simon, Sarah F. Smithson, Carlo Marcelis, Bronwyn Kerr, Jill Clayton‐Smith, Esther Kinning, Sahar Mansour, Frances Elmslie, Linda Goodwin, Annemarie H. van der Hout, Hermine E. Veenstra‐Knol, Johanna C. Herkert, Allan M. Lund, Raoul C. M. Hennekam, André Mégarbané, Melissa M. Lees, Louise C. Wilson, Alison Male, Jane Hurst, Yasemin Alanay, Göran Annerén, Regina C. Betz, Ernie M. H. F. Bongers, Valerie Cormier‐Daire, Anne Dieux, Albert David, Mariet W. Elting, Jenneke van den Ende, Andrew Green, Johanna M. van Hagen, Niels Thomas Hertel, Muriel Holder‐Espinasse, Nicolette den Hollander, Tessa Homfray, Hanne D. Hove, Susan Price, Annick Raas‐Rothschild, Marianne Rohrbach, Barbara Schroeter, Mohnish Suri, Elizabeth M. Thompson, Edward S. Tobias, Annick Toutain, Maaike Vreeburg, Emma Wakeling, Nine V. Knoers, Paul Coucke, and Geert R. Mortier. A study of the clinical and radiological features in a cohort of 93 patients with a col2a1 mutation causing spondyloepiphyseal dysplasia congenita or a related phenotype. American Journal of Medical Genetics Part A, 167:461-475, Mar 2015. URL: https://doi.org/10.1002/ajmg.a.36922, doi:10.1002/ajmg.a.36922. This article has 105 citations.

17. (aljuid2026col2a1mutationsand pages 6-7): Latifa Mohammed Aljuid, Dareen Alyousfi, Manal Hosawi, and Ayman Z Elsamanoudy. Col2a1 mutations and type ii collagenopathies: molecular mechanisms and ipsc-based modeling of cartilage disorders. Archives of Stem Cell and Therapy, 6:6, Feb 2026. URL: https://doi.org/10.46439/stemcell.6.026, doi:10.46439/stemcell.6.026. This article has 0 citations.

18. (barathouari2016theexpandingspectrum pages 1-2): Mouna Barat-Houari, Bruno Dumont, Aurélie Fabre, Frédéric TM Them, Yves Alembik, Jean-Luc Alessandri, Jeanne Amiel, Séverine Audebert, Clarisse Baumann-Morel, Patricia Blanchet, Eric Bieth, Marie Brechard, Tiffany Busa, Patrick Calvas, Yline Capri, François Cartault, Nicolas Chassaing, Vidrica Ciorca, Christine Coubes, Albert David, Anne-Lise Delezoide, Delphine Dupin-Deguine, Salima El Chehadeh, Laurence Faivre, Fabienne Giuliano, Alice Goldenberg, Bertrand Isidor, Marie-Line Jacquemont, Sophie Julia, Josseline Kaplan, Didier Lacombe, Marine Lebrun, Sandrine Marlin, Dominique Martin-Coignard, Jelena Martinovic, Alice Masurel, Judith Melki, Monique Mozelle-Nivoix, Karine Nguyen, Sylvie Odent, Nicole Philip, Lucile Pinson, Ghislaine Plessis, Chloé Quélin, Elise Shaeffer, Sabine Sigaudy, Christel Thauvin, Marianne Till, Renaud Touraine, Jacqueline Vigneron, Geneviève Baujat, Valérie Cormier-Daire, Martine Le Merrer, David Geneviève, and Isabelle Touitou. The expanding spectrum of col2a1 gene variants in 136 patients with a skeletal dysplasia phenotype. European Journal of Human Genetics, 24:992-1000, Dec 2016. URL: https://doi.org/10.1038/ejhg.2015.250, doi:10.1038/ejhg.2015.250. This article has 54 citations and is from a domain leading peer-reviewed journal.