COL11A2-Related Hearing Loss — Comprehensive Disease Characteristics Report

Target disease

Disease name: COL11A2-Related Hearing Loss (Mendelian; spectrum includes nonsyndromic and syndromic presentations) (mcguirt1999mutationsincol11a2 pages 1-2, chen2005mutationofcol11a2 pages 2-5, iwasa2015nonocularsticklersyndrome pages 3-4).

Note on identifiers: In the evidence retrieved in this run, authoritative ontology/disease-resource identifiers (MONDO, Orphanet, ICD-10/11, MeSH, OMIM IDs) were not directly available; therefore this report anchors the condition to well-established deafness locus identifiers DFNA13 (autosomal dominant) and DFNB53 (autosomal recessive), and to COL11A2-related non-ocular Stickler syndrome / Stickler syndrome type 3 and OSMED as described in the clinical genetics literature (mcguirt1999mutationsincol11a2 pages 1-2, chen2005mutationofcol11a2 pages 2-5, iwasa2015nonocularsticklersyndrome pages 3-4, acke2022hearinglossin pages 4-6).

1. Disease information

1.1 Definition and current understanding

COL11A2-related hearing loss refers to hereditary hearing impairment caused by pathogenic variants in COL11A2, encoding the α2 chain of type XI collagen, an extracellular-matrix (ECM) fibrillar collagen that contributes to cochlear structures including the tectorial membrane (TM) (masaki2009col11a2deletionreveals pages 1-2, sellon2019thetectorialmembrane pages 1-3).

Clinically, COL11A2 pathogenic variants can cause: - Autosomal dominant nonsyndromic hearing loss (DFNA13) (mcguirt1999mutationsincol11a2 pages 1-2, mcguirt1999mutationsincol11a2 pages 5-6). - Autosomal recessive nonsyndromic hearing loss (DFNB53) (chen2005mutationofcol11a2 pages 2-5). - Syndromic disease with hearing loss, including COL11A2-related non-ocular Stickler syndrome (Stickler syndrome type 3) and COL11A2-associated skeletal dysplasias (e.g., OSMED) in the broader disease spectrum (iwasa2015nonocularsticklersyndrome pages 3-4, acke2022hearinglossin pages 4-6, chen2005mutationofcol11a2 pages 2-5).

1.2 Common synonyms / alternative names

• DFNA13 (COL11A2-related autosomal dominant nonsyndromic hearing loss) (mcguirt1999mutationsincol11a2 pages 1-2).
• DFNB53 (COL11A2-related autosomal recessive nonsyndromic hearing loss) (chen2005mutationofcol11a2 pages 2-5).
• Non-ocular Stickler syndrome / Stickler syndrome type 3 (COL11A2-related) (iwasa2015nonocularsticklersyndrome pages 3-4, acke2022hearinglossin pages 4-6).
• OSMED (otospondylomegaepiphyseal dysplasia) in the COL11A2 phenotypic spectrum (chen2005mutationofcol11a2 pages 2-5, acke2022hearinglossin pages 4-6).

1.3 Evidence source type

The information summarized here is derived from aggregated disease-level reviews plus individual/family-level primary clinical genetics reports, and animal model/mechanistic studies (acke2022hearinglossin pages 4-6, acke2012hearingimpairmentin pages 10-10, mcguirt1999mutationsincol11a2 pages 1-2, chen2005mutationofcol11a2 pages 2-5, masaki2009col11a2deletionreveals pages 1-2).

2. Etiology

2.1 Disease causal factors (genetic)

Primary cause: germline pathogenic variants in COL11A2 (mcguirt1999mutationsincol11a2 pages 1-2, chen2005mutationofcol11a2 pages 2-5, iwasa2015nonocularsticklersyndrome pages 3-4).

Inheritance: - Autosomal dominant (AD): DFNA13; also AD non-ocular Stickler syndrome reported with COL11A2 variants (mcguirt1999mutationsincol11a2 pages 1-2, iwasa2015nonocularsticklersyndrome pages 3-4). - Autosomal recessive (AR): DFNB53 (chen2005mutationofcol11a2 pages 2-5).

Pathogenic variant examples (from primary studies): - DFNA13 (AD): p.Arg549Cys and p.Gly323Glu (McGuirt et al., 1999; DOI: https://doi.org/10.1038/70516; publication month/year: Dec 1999) (mcguirt1999mutationsincol11a2 pages 1-2, mcguirt1999mutationsincol11a2 pages 4-5). - DFNB53 (AR): p.Pro621Thr (Chen et al., 2005; DOI: https://doi.org/10.1136/jmg.2005.032615; Oct 2005) (chen2005mutationofcol11a2 pages 2-5). - Non-ocular Stickler syndrome (AD) example: a COL11A2 frameshift deletion reported as p.1312_1315del4 (Iwasa et al., 2015; DOI: https://doi.org/10.1177/0003489415575044; Mar 2015) (iwasa2015nonocularsticklersyndrome pages 3-4).

2.2 Variant type and functional consequences (current evidence)

• Missense substitutions in the collagen triple-helix domain are implicated in DFNA13 and DFNB53 (mcguirt1999mutationsincol11a2 pages 1-2, chen2005mutationofcol11a2 pages 2-5).
• A frameshift variant was reported in a family with AD non-ocular Stickler syndrome and hearing loss (iwasa2015nonocularsticklersyndrome pages 3-4).
• In a Col11a2-null mouse model, loss of type XI collagen perturbs TM collagen organization and TM mechanical anisotropy, consistent with a structural/biomechanical mechanism (masaki2009col11a2deletionreveals pages 1-2).

2.3 Risk factors / protective factors / gene–environment interactions

For this Mendelian disorder, genotype is the dominant determinant; the retrieved sources did not provide human data on environmental risk modifiers or protective factors specific to COL11A2-related hearing loss.

Nevertheless, recent experimental cochlear proteomics suggests that noise exposure can perturb ECM/collagen proteins including COL11A2, implicating ECM remodeling as a shared axis for genetic and environmental injury to hearing (Shi et al., 2023; DOI: https://doi.org/10.1007/s12033-022-00557-2; Oct 2023) (shi2023acutenoisecauses pages 1-4, shi2023acutenoisecauses pages 13-19).

3. Phenotypes

3.1 Core hearing phenotypes (human)

DFNA13 (COL11A2; AD nonsyndromic)

• Onset: congenital (mcguirt1999mutationsincol11a2 pages 1-2).
• Progression: reported as non-progressive (mcguirt1999mutationsincol11a2 pages 1-2, mcguirt1999mutationsincol11a2 pages 5-6).
• Audiogram: predominantly mid-frequency loss with a characteristic “cookie-bite” profile (mcguirt1999mutationsincol11a2 pages 1-2).
• Severity: mild to moderately severe in a reported family (mcguirt1999mutationsincol11a2 pages 1-2).
• Extra-auditory features: absent in the described nonsyndromic families.
• Direct quote: “Specifically, no midface hypoplasia, cleft palate, precocious arthritis, or stature or ocular abnormalities were noted.” (mcguirt1999mutationsincol11a2 pages 1-2).

Suggested HPO terms (core hearing): - Sensorineural hearing impairment (HP:0000407) - Mid-frequency hearing loss (HP:0040117) (if curated as audiogram phenotype) - Congenital onset (HP:0003577) - Non-progressive (HP:0003680)

DFNB53 (COL11A2; AR nonsyndromic)

• Onset: prelingual (chen2005mutationofcol11a2 pages 2-5).
• Severity: profound sensorineural hearing loss (chen2005mutationofcol11a2 pages 2-5).
• Progression: described as non-progressive (chen2005mutationofcol11a2 pages 2-5).
• Vestibular: normal on clinical assessment (chen2005mutationofcol11a2 pages 2-5).
• Extra-auditory: in the reported family, no ocular/midface/palatal abnormalities or skeletal dysplasia, supporting a nonsyndromic diagnosis (chen2005mutationofcol11a2 pages 2-5).

Suggested HPO terms: - Sensorineural hearing impairment (HP:0000407) - Profound hearing impairment (HP:0000405) - Prelingual onset (HP:0003623)

COL11A2-related non-ocular Stickler syndrome (Stickler type 3)

A Japanese family report and a Stickler-focused review indicate that COL11A2-related Stickler phenotypes are frequently associated with hearing loss: - Frequency in non-ocular Stickler (as stated in the family report): “94.1% of non-ocular Stickler syndrome patients have hearing loss.” (iwasa2015nonocularsticklersyndrome pages 3-4). - Course: in the reported family, childhood-onset, slowly progressive, mild-to-moderate hearing loss with good speech discrimination and benefit from hearing aids (iwasa2015nonocularsticklersyndrome pages 3-4). - Review-level audiogram pattern (Stickler type 2/3): mild–moderate low/mid-frequency loss and moderate–severe high-frequency loss; U-shaped patterns reported in some cases (acke2022hearinglossin pages 4-6).

Suggested HPO terms (Stickler-related): - Sensorineural hearing impairment (HP:0000407) - Progressive hearing impairment (HP:0001730) - Midface hypoplasia (HP:0000347)

3.2 Quality of life impact

Specific validated QoL instrument data (e.g., SF-36, EQ-5D, PROMIS) were not present in the retrieved evidence. However, because Stickler syndrome involves multisystem features (including vision impairment in many types), a 2012 systematic review emphasized the importance of auditory follow-up. - Direct quote from abstract: “Hearing impairment in patients with Stickler syndrome is common. … Regular auditory follow-up is strongly advised, particularly because many Stickler patients are visually impaired.” (Acke et al., 2012; DOI: https://doi.org/10.1186/1750-1172-7-84; Oct 2012) (acke2012hearingimpairmentin pages 10-10).

4. Genetic / molecular information

4.1 Causal gene

• COL11A2 (collagen type XI alpha 2 chain) (mcguirt1999mutationsincol11a2 pages 1-2, chen2005mutationofcol11a2 pages 2-5).

4.2 Pathogenic variants and genotype–phenotype correlation (evidence-based)

• AD DFNA13 can be caused by heterozygous missense variants and presents as isolated nonsyndromic hearing loss with cookie-bite audiograms (mcguirt1999mutationsincol11a2 pages 1-2, mcguirt1999mutationsincol11a2 pages 4-5).
• AR DFNB53 in one consanguineous family was caused by a homozygous missense variant p.Pro621Thr and caused profound prelingual nonsyndromic SNHL without skeletal/ocular findings (chen2005mutationofcol11a2 pages 2-5).
• In a COL11A2-related non-ocular Stickler family, massively parallel sequencing enabled detection of a novel variant, supporting broad use of NGS-based testing in heterogeneous hereditary hearing loss (iwasa2015nonocularsticklersyndrome pages 3-4).

4.3 Modifier genes / epigenetics / chromosomal abnormalities

No COL11A2-specific modifier-gene or epigenetic-disease mechanisms were described in the retrieved evidence.

5. Environmental information

5.1 Noise exposure as an ECM perturbagen (relevant to hearing loss biology)

While not evidence for causation in COL11A2 Mendelian disease, a recent cochlear proteomics study provides mechanistic context for ECM vulnerability: - In an acute impulse-noise guinea pig model, COL11A2 (along with other ECM proteins) was among hearing-related proteins that changed after noise exposure (shi2023acutenoisecauses pages 1-4, shi2023acutenoisecauses pages 13-19). - ABR threshold shift (example statistic): click threshold increased from 26.88 ± 8.08 dB (pre) to 57.00 ± 6.78 dB (day 1), with partial recovery by day 7 (shi2023acutenoisecauses pages 13-19). - The authors conclude: “Impulse noise can affect the expression of differential proteins through focal adhesion pathways.” (shi2023acutenoisecauses pages 1-4).

Implication: ECM/focal-adhesion signaling changes provide a plausible intersection between ECM structural genes (e.g., COL11A2) and acquired cochlear injury pathways, though direct gene–environment interaction data in humans were not retrieved (shi2023acutenoisecauses pages 10-13, shi2023acutenoisecauses pages 1-4).

6. Mechanism / pathophysiology

6.1 Mechanistic concept: “cochlear conductive” / ECM-biomechanical hearing loss

A COL11A2-related non-ocular Stickler report emphasizes that COL11A2 is expressed in the tectorial membrane, and frames the impairment as potentially due to altered sound transmission within the cochlea (“cochlear conductive hearing loss”) rather than primary hair cell expression (iwasa2015nonocularsticklersyndrome pages 4-5).

6.2 Tectorial membrane (TM) mechanics and COL11A2

A key mechanistic study demonstrated that Col11a2 deletion changes TM collagen architecture and collapses mechanical anisotropy: - Functional impact: DPOAE and ABR were reduced by approximately 30–50 dB across frequencies (masaki2009col11a2deletionreveals pages 1-2). - Mechanical impact: radial shear impedance decreased by 5.5 ± 0.8 dB and longitudinal shear impedance by 3.3 ± 0.3 dB; the radial-to-longitudinal impedance ratio fell from 1.8 ± 0.7 (WT) to 1.0 ± 0.1 (Col11a2−/−) (Masaki et al., 2009; DOI: https://doi.org/10.1016/j.bpj.2009.02.056; Jun 2009) (masaki2009col11a2deletionreveals pages 1-2, masaki2009col11a2deletionreveals media 7efb6948).

Causal chain (evidence-backed): COL11A2 pathogenic variant or loss → abnormal type XI collagen contribution to TM radial collagen fibrils → altered TM anisotropy/coupling and cochlear micromechanics → elevated auditory thresholds and characteristic audiometric patterns (especially mid-frequency deficits in DFNA13) (masaki2009col11a2deletionreveals pages 1-2, mcguirt1999mutationsincol11a2 pages 1-2).

6.3 Developmental expression and implicated cochlear cell types

In situ hybridization in developing mouse cochlea localized Col11a1/Col11a2 mRNA primarily to epithelial ridge and lateral wall structures that contribute to TM and cochlear ECM: - Greater epithelial ridge as main source contributing to TM; later localization includes inner sulcus, Claudius’ cells, and Boettcher’s cells (Shpargel et al., 2004; DOI: https://doi.org/10.1080/00016480410016162; Mar 2004) (shpargel2004col11a1andcol11a2 pages 1-3, shpargel2004col11a1andcol11a2 pages 3-4). - No hybridization detected in hair cells (shpargel2004col11a1andcol11a2 pages 3-4).

Suggested ontology mappings: - GO Biological Process: extracellular matrix organization (GO:0030198); collagen fibril organization (GO:0030199) - GO Cellular Component: tectorial membrane (GO:0060089) (if used in a curated set); extracellular matrix (GO:0031012) - Uberon anatomical structures: cochlea (UBERON:0001767); tectorial membrane (UBERON:0004953) - Cell Ontology (examples aligned to cited structures): epithelial cell (CL:0000066) for ridge/sulcus epithelia; fibroblast (CL:0000057) relevant to spiral ligament ECM production (note: the retrieved expression study names specific cochlear epithelial regions but does not provide CL identifiers) (shpargel2004col11a1andcol11a2 pages 3-4).

7. Anatomical structures affected

Primary: inner ear/cochlea, especially ECM structures controlling micromechanics: the tectorial membrane (masaki2009col11a2deletionreveals pages 1-2).

UBERON suggestions: cochlea (UBERON:0001767); organ of Corti (UBERON:0001890); tectorial membrane (UBERON:0004953).

8. Temporal development (natural history)

DFNA13

Congenital onset and non-progressive course were reported in DFNA13 families (mcguirt1999mutationsincol11a2 pages 1-2).

DFNB53

Prelingual onset and non-progressive course were described in DFNB53 family L622 (chen2005mutationofcol11a2 pages 2-5).

COL11A2-related non-ocular Stickler syndrome

In one family: childhood-onset and slowly progressive hearing loss (iwasa2015nonocularsticklersyndrome pages 3-4). In Stickler type 2/3 review synthesis, onset is “early” and losses may be missed by newborn screening if mild (acke2022hearinglossin pages 4-6).

9. Inheritance and population

9.1 Inheritance patterns

• DFNA13: autosomal dominant (mcguirt1999mutationsincol11a2 pages 1-2).
• DFNB53: autosomal recessive (chen2005mutationofcol11a2 pages 2-5).

9.2 Population genetics / epidemiology

No prevalence/incidence estimates specific to COL11A2-related hearing loss were available in the retrieved evidence. However, a Stickler systematic review quantified hearing loss across Stickler syndrome case literature: - Direct quote from abstract: “Hearing loss was found in 62.9% [of Stickler syndrome patients], mostly mild to moderate when reported.” (Acke et al., 2012; DOI: https://doi.org/10.1186/1750-1172-7-84; Oct 2012) (acke2012hearingimpairmentin pages 10-10).

10. Diagnostics

10.1 Clinical tests

• Pure-tone audiometry used to confirm and characterize hearing loss in DFNB53 and Stickler/non-ocular Stickler (chen2005mutationofcol11a2 pages 2-5, iwasa2015nonocularsticklersyndrome pages 3-4).
• Speech discrimination testing and observed benefit from amplification were reported in COL11A2-related non-ocular Stickler (iwasa2015nonocularsticklersyndrome pages 3-4).

10.2 Genetic testing

• Massively parallel sequencing (NGS) enabled diagnosis of non-ocular Stickler syndrome in a Japanese hearing-loss cohort/family and facilitated correct clinical classification (e.g., distinguishing from other craniofacial conditions) (iwasa2015nonocularsticklersyndrome pages 3-4).

10.3 Differential diagnosis

The non-ocular Stickler report describes clinical confusion with Binder syndrome due to orofacial appearance, highlighting the role of genomic testing for correct syndromic diagnosis (iwasa2015nonocularsticklersyndrome pages 3-4).

11. Outcome / prognosis

Human survival/mortality endpoints are not relevant/available in the retrieved evidence; the primary morbidity is hearing impairment and (in syndromic forms) connective-tissue manifestations. Prognosis for hearing stability varies by entity: non-progressive DFNA13 and DFNB53 in cited families vs slowly progressive hearing loss in a non-ocular Stickler family report (mcguirt1999mutationsincol11a2 pages 1-2, chen2005mutationofcol11a2 pages 2-5, iwasa2015nonocularsticklersyndrome pages 3-4).

12. Treatment

12.1 Current applications and real-world implementations

Hearing rehabilitation (amplification): - In an AD COL11A2-related non-ocular Stickler family, patients used hearing aids with favorable speech discrimination outcomes, and the authors recommended hearing aids as appropriate management (Iwasa et al., 2015; DOI: https://doi.org/10.1177/0003489415575044; Mar 2015) (iwasa2015nonocularsticklersyndrome pages 3-4).

Cochlear implantation: No cochlear implant outcome data were present in the retrieved evidence for COL11A2-specific hearing loss.

MAXO suggestions: - Hearing aid therapy (MAXO:0000605) (term suggestion; MAXO ID may require verification in a MAXO browser).

12.2 Emerging / experimental therapies

No COL11A2-specific interventional clinical trials were identified in the retrieved clinical-trials search during this run.

A 2023 cochlear single-cell atlas emphasizes translational motivation for gene-specific targeted therapies in hereditary deafness generally: - Direct quote from abstract/significance: “One major challenge is the implementation of these therapies for diverse isolated and syndromic forms of hearing loss, taking into account the spatial and temporal patterns of expression of the causal gene…” (Jean et al., 2023; DOI: https://doi.org/10.1073/pnas.2221744120; Jun 2023) (jean2023singlecelltranscriptomicprofiling pages 6-7).

13. Prevention

No COL11A2-specific prevention trials or environmental prevention strategies were described in the retrieved evidence. For Mendelian disease, prevention is typically via genetic counseling and reproductive options; however, detailed guidance documents were not retrieved in this run.

14. Other species / natural disease

No naturally occurring veterinary COL11A2 hearing-loss syndromes were retrieved.

15. Model organisms

Mouse models: - Col11a2 knockout/deletion models show auditory threshold elevations and TM collagen disorganization (mcguirt1999mutationsincol11a2 pages 5-6, masaki2009col11a2deletionreveals pages 1-2). - Mechanistic TM study quantified loss of anisotropy and associated ABR/DPOAE reductions (masaki2009col11a2deletionreveals pages 1-2).

Zebrafish (non-hearing phenotype in retrieved evidence): - A 2023 study used CRISPR zebrafish col11a2 loss-of-function for vertebral development; it supports broader COL11A2 roles in cartilage/ECM but does not provide hearing phenotypes in the excerpted evidence (shi2023acutenoisecauses pages 10-13).

Key recent developments (prioritizing 2023–2024 sources)

1. ECM proteomics in noise injury implicates COL11A2 among hearing-relevant ECM proteins and provides quantitative ABR threshold shifts and pathway enrichment (focal adhesion/ECM receptor interaction) (Shi et al., 2023; Oct 2023; https://doi.org/10.1007/s12033-022-00557-2) (shi2023acutenoisecauses pages 1-4, shi2023acutenoisecauses pages 13-19).
2. Single-cell/single-nucleus cochlear atlases for targeted therapies provide frameworks to map expression patterns of hereditary deafness genes (not COL11A2-specific in the excerpt) (Jean et al., 2023; Jun 2023; https://doi.org/10.1073/pnas.2221744120) (jean2023singlecelltranscriptomicprofiling pages 6-7).

Expert synthesis / interpretation (grounded in retrieved sources)

The most coherent mechanistic model supported by both human genetics and animal biophysics is that many COL11A2-related hearing phenotypes arise from ECM structural defects in the tectorial membrane, altering cochlear mechanics rather than primary hair-cell dysfunction. This aligns: (i) with developmental expression patterns that do not localize Col11a2 mRNA to hair cells (shpargel2004col11a1andcol11a2 pages 3-4), (ii) with TM mechanical anisotropy collapse and large threshold shifts in Col11a2−/− mice (masaki2009col11a2deletionreveals pages 1-2), and (iii) with the characteristic mid-frequency “cookie-bite” audiograms in DFNA13 families (mcguirt1999mutationsincol11a2 pages 1-2).

Structured summary table

Table: This table summarizes the main COL11A2-associated hearing loss entities across nonsyndromic and syndromic presentations, highlighting inheritance, representative variants, phenotype patterns, extra-auditory findings, and cochlear ECM/tectorial membrane mechanisms. It is useful as a compact genotype-phenotype reference for knowledge-base curation.

Supporting figure (tectorial membrane anisotropy)

A cropped panel from Masaki et al. (2009) illustrates the shear impedance changes underlying the loss of TM anisotropy in Col11a2−/− mice (masaki2009col11a2deletionreveals media 7efb6948).

Limitations of this report (evidence gaps in this run)

• MONDO/Orphanet/OMIM/ICD/MeSH identifiers were not retrieved via available tools in this run.
• Epidemiology (population prevalence/incidence), penetrance/expressivity estimates, carrier frequency (gnomAD), and comprehensive COL11A2 variant catalogs (ClinVar) were not available in the retrieved evidence set.
• Clinical management beyond hearing aids (e.g., cochlear implant outcomes) and formal QoL statistics were not retrieved.

References

1. (mcguirt1999mutationsincol11a2 pages 1-2): Wyman T. McGuirt, Sai D. Prasad, Andrew J. Griffith, Henricus P.M. Kunst, Glenn E. Green, Karl B. Shpargel, Christina Runge, Christy Huybrechts, Robert F. Mueller, Eric Lynch, Mary-Claire King, Han G. Brunner, Cor W.R.J. Cremers, Masamine Takanosu, Shi-Wu Li, Machiko Arita, Richard Mayne, Darwin J. Prockop, Guy Van Camp, and Richard J.H. Smith. Mutations in col11a2 cause non-syndromic hearing loss (dfna13). Nature Genetics, 23:413-419, Dec 1999. URL: https://doi.org/10.1038/70516, doi:10.1038/70516. This article has 347 citations and is from a highest quality peer-reviewed journal.

2. (chen2005mutationofcol11a2 pages 2-5): Wenjie Chen, K. Kahrizi, N. Meyer, Y. Riazalhosseini, Guy, Van Camp, H. Najmabadi, and R. J. Smith. Mutation of col11a2 causes autosomal recessive non-syndromic hearing loss at the dfnb53 locus. Journal of Medical Genetics, 42:e61-e61, Oct 2005. URL: https://doi.org/10.1136/jmg.2005.032615, doi:10.1136/jmg.2005.032615. This article has 106 citations and is from a domain leading peer-reviewed journal.

3. (iwasa2015nonocularsticklersyndrome pages 3-4): Yoh-ichiro Iwasa, Hideaki Moteki, Mitsuru Hattori, Ririko Sato, Shin-ya Nishio, Yutaka Takumi, and Shin-ichi Usami. Non-ocular stickler syndrome with a novel mutation in col11a2 diagnosed by massively parallel sequencing in japanese hearing loss patients. Annals of Otology, Rhinology & Laryngology, 124:111S-117S, Mar 2015. URL: https://doi.org/10.1177/0003489415575044, doi:10.1177/0003489415575044. This article has 10 citations.

4. (acke2022hearinglossin pages 4-6): Frederic R. E. Acke and Els M. R. De Leenheer. Hearing loss in stickler syndrome: an update. Genes, 13:1571, Sep 2022. URL: https://doi.org/10.3390/genes13091571, doi:10.3390/genes13091571. This article has 28 citations.

5. (masaki2009col11a2deletionreveals pages 1-2): Kinuko Masaki, Kinuko Masaki, J. Gu, J. Gu, R. Ghaffari, R. Ghaffari, Gary Chan, Richard J. H. Smith, D. M. Freeman, D. M. Freeman, and A. Aranyosi. Col11a2 deletion reveals the molecular basis for tectorial membrane mechanical anisotropy. Biophysical Journal, 96:4717-4724, Jun 2009. URL: https://doi.org/10.1016/j.bpj.2009.02.056, doi:10.1016/j.bpj.2009.02.056. This article has 35 citations and is from a domain leading peer-reviewed journal.

6. (sellon2019thetectorialmembrane pages 1-3): Jonathan B. Sellon, Roozbeh Ghaffari, and Dennis M. Freeman. The tectorial membrane: mechanical properties and functions. Cold Spring Harbor perspectives in medicine, 9:a033514, Oct 2019. URL: https://doi.org/10.1101/cshperspect.a033514, doi:10.1101/cshperspect.a033514. This article has 34 citations and is from a peer-reviewed journal.

7. (mcguirt1999mutationsincol11a2 pages 5-6): Wyman T. McGuirt, Sai D. Prasad, Andrew J. Griffith, Henricus P.M. Kunst, Glenn E. Green, Karl B. Shpargel, Christina Runge, Christy Huybrechts, Robert F. Mueller, Eric Lynch, Mary-Claire King, Han G. Brunner, Cor W.R.J. Cremers, Masamine Takanosu, Shi-Wu Li, Machiko Arita, Richard Mayne, Darwin J. Prockop, Guy Van Camp, and Richard J.H. Smith. Mutations in col11a2 cause non-syndromic hearing loss (dfna13). Nature Genetics, 23:413-419, Dec 1999. URL: https://doi.org/10.1038/70516, doi:10.1038/70516. This article has 347 citations and is from a highest quality peer-reviewed journal.

8. (acke2012hearingimpairmentin pages 10-10): Frederic R E Acke, Ingeborg J M Dhooge, Fransiska Malfait, and Els M R De Leenheer. Hearing impairment in stickler syndrome: a systematic review. Orphanet Journal of Rare Diseases, 7:84-84, Oct 2012. URL: https://doi.org/10.1186/1750-1172-7-84, doi:10.1186/1750-1172-7-84. This article has 127 citations and is from a peer-reviewed journal.

9. (mcguirt1999mutationsincol11a2 pages 4-5): Wyman T. McGuirt, Sai D. Prasad, Andrew J. Griffith, Henricus P.M. Kunst, Glenn E. Green, Karl B. Shpargel, Christina Runge, Christy Huybrechts, Robert F. Mueller, Eric Lynch, Mary-Claire King, Han G. Brunner, Cor W.R.J. Cremers, Masamine Takanosu, Shi-Wu Li, Machiko Arita, Richard Mayne, Darwin J. Prockop, Guy Van Camp, and Richard J.H. Smith. Mutations in col11a2 cause non-syndromic hearing loss (dfna13). Nature Genetics, 23:413-419, Dec 1999. URL: https://doi.org/10.1038/70516, doi:10.1038/70516. This article has 347 citations and is from a highest quality peer-reviewed journal.

10. (shi2023acutenoisecauses pages 1-4): Min Shi, Lei Cao, Daxiong Ding, Lei Shi, Yiyong Hu, Guowei Qi, Li Zhan, Yuhua Zhu, Wenxing Yu, Ping Lv, and Ning Yu. Acute noise causes down-regulation of ecm protein expression in guinea pig cochlea. Molecular Biotechnology, 65:774-785, Oct 2023. URL: https://doi.org/10.1007/s12033-022-00557-2, doi:10.1007/s12033-022-00557-2. This article has 5 citations and is from a peer-reviewed journal.

11. (shi2023acutenoisecauses pages 13-19): Min Shi, Lei Cao, Daxiong Ding, Lei Shi, Yiyong Hu, Guowei Qi, Li Zhan, Yuhua Zhu, Wenxing Yu, Ping Lv, and Ning Yu. Acute noise causes down-regulation of ecm protein expression in guinea pig cochlea. Molecular Biotechnology, 65:774-785, Oct 2023. URL: https://doi.org/10.1007/s12033-022-00557-2, doi:10.1007/s12033-022-00557-2. This article has 5 citations and is from a peer-reviewed journal.

12. (shi2023acutenoisecauses pages 10-13): Min Shi, Lei Cao, Daxiong Ding, Lei Shi, Yiyong Hu, Guowei Qi, Li Zhan, Yuhua Zhu, Wenxing Yu, Ping Lv, and Ning Yu. Acute noise causes down-regulation of ecm protein expression in guinea pig cochlea. Molecular Biotechnology, 65:774-785, Oct 2023. URL: https://doi.org/10.1007/s12033-022-00557-2, doi:10.1007/s12033-022-00557-2. This article has 5 citations and is from a peer-reviewed journal.

13. (iwasa2015nonocularsticklersyndrome pages 4-5): Yoh-ichiro Iwasa, Hideaki Moteki, Mitsuru Hattori, Ririko Sato, Shin-ya Nishio, Yutaka Takumi, and Shin-ichi Usami. Non-ocular stickler syndrome with a novel mutation in col11a2 diagnosed by massively parallel sequencing in japanese hearing loss patients. Annals of Otology, Rhinology & Laryngology, 124:111S-117S, Mar 2015. URL: https://doi.org/10.1177/0003489415575044, doi:10.1177/0003489415575044. This article has 10 citations.

14. (masaki2009col11a2deletionreveals media 7efb6948): Kinuko Masaki, Kinuko Masaki, J. Gu, J. Gu, R. Ghaffari, R. Ghaffari, Gary Chan, Richard J. H. Smith, D. M. Freeman, D. M. Freeman, and A. Aranyosi. Col11a2 deletion reveals the molecular basis for tectorial membrane mechanical anisotropy. Biophysical Journal, 96:4717-4724, Jun 2009. URL: https://doi.org/10.1016/j.bpj.2009.02.056, doi:10.1016/j.bpj.2009.02.056. This article has 35 citations and is from a domain leading peer-reviewed journal.

15. (shpargel2004col11a1andcol11a2 pages 1-3): Karl B. Shpargel, Tomoko Makishima, and Andrew J. Griffith. Col11a1 and col11a2 mrna expression in the developing mouse cochlea: implications for the correlation of hearing loss phenotype with mutant type xi collagen genotype. Acta Oto-Laryngologica, 124:242-248, Mar 2004. URL: https://doi.org/10.1080/00016480410016162, doi:10.1080/00016480410016162. This article has 46 citations and is from a peer-reviewed journal.

16. (shpargel2004col11a1andcol11a2 pages 3-4): Karl B. Shpargel, Tomoko Makishima, and Andrew J. Griffith. Col11a1 and col11a2 mrna expression in the developing mouse cochlea: implications for the correlation of hearing loss phenotype with mutant type xi collagen genotype. Acta Oto-Laryngologica, 124:242-248, Mar 2004. URL: https://doi.org/10.1080/00016480410016162, doi:10.1080/00016480410016162. This article has 46 citations and is from a peer-reviewed journal.

17. (jean2023singlecelltranscriptomicprofiling pages 6-7): Philippe Jean, Fabienne Wong Jun Tai, Amrit Singh-Estivalet, Andrea Lelli, Cyril Scandola, Sébastien Megharba, Sandrine Schmutz, Solène Roux, Sabrina Mechaussier, Muriel Sudres, Enguerran Mouly, Anne-Valérie Heritier, Crystel Bonnet, Adeline Mallet, Sophie Novault, Valentina Libri, Christine Petit, and Nicolas Michalski. Single-cell transcriptomic profiling of the mouse cochlea: an atlas for targeted therapies. Proceedings of the National Academy of Sciences of the United States of America, Jun 2023. URL: https://doi.org/10.1073/pnas.2221744120, doi:10.1073/pnas.2221744120. This article has 65 citations and is from a highest quality peer-reviewed journal.