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: Dacryocystitis-Osteopoikilosis Syndrome
• MONDO ID: (if available)
• Category: Mendelian

Research Objectives

Please provide a comprehensive research report on the pathophysiology of Dacryocystitis-Osteopoikilosis Syndrome. 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

Pathophysiology Research Report: Dacryocystitis–Osteopoikilosis Syndrome (Günal–Seber–Başaran syndrome)

0. Disease identity and scope

Disease: Dacryocystitis–osteopoikilosis syndrome (also referred to as Günal–Seber–Başaran syndrome). The disease is represented in MONDO as MONDO_0008158 (“dacryocystitis-osteopoikilosis syndrome”) and in Orphanet as Orphanet_1562 (“Dacryocystitis – osteopoikilosis”). (OpenTargets Search: Dacryocystitis-osteopoikilosis syndrome,Osteopoikilosis,Buschke-Ollendorff syndrome)

Clinical definition (core): Familial osteopoikilosis (multiple periarticular sclerotic foci) plus chronic dacryocystitis, thought to arise from lacrimal drainage stenosis. The original description is a multigenerational pedigree with five affected family members in which chronic dacryocystitis was confirmed by lacrimal lavage and dacryocystography alongside radiographic osteopoikilosis. (gunal1993dacryocystitisassociatedwith pages 1-3)

Interpretation for pathophysiology: Direct mechanistic studies in “dacryocystitis–osteopoikilosis syndrome” per se are sparse; therefore, current understanding largely derives from (i) the original pedigree-based description of the combined phenotype and proposed local mechanism for dacryocystitis, and (ii) robust genetic/mechanistic work defining the molecular basis of osteopoikilosis/Buschke–Ollendorff syndrome (BOS) due to LEMD3/MAN1 loss-of-function and dysregulated TGF-β/BMP–SMAD signaling. (gunal1993dacryocystitisassociatedwith pages 1-3, hellemans2004lossoffunctionmutationsin pages 3-4)

Table: This table summarizes primary literature characterizing the clinical entity (Gunal-Seber-Basaran syndrome), the established molecular cause (LEMD3 loss-of-function), and proposed mechanisms linking osteosclerosis to soft tissue stenosis.

1. Core pathophysiology (molecular → cellular → tissue)

1.1 Primary pathophysiological mechanisms

Primary molecular defect (best-supported across the spectrum): Osteopoikilosis (and the closely related BOS phenotype) is caused by heterozygous loss-of-function mutations in LEMD3 (also known as MAN1), which encodes an inner nuclear membrane protein whose C-terminal region binds receptor-activated SMADs and antagonizes TGF-β and BMP signaling. (hellemans2004lossoffunctionmutationsin pages 3-4, hellemans2004lossoffunctionmutationsin pages 1-2, mortier2014traumaticfracturein pages 2-3)

Dominant inheritance model: Human genetic evidence supports monoallelic (autosomal dominant) inheritance for osteopoikilosis and BOS, consistent with haploinsufficiency or functional truncation of MAN1/LEMD3. (hellemans2004lossoffunctionmutationsin pages 3-4, OpenTargets Search: Dacryocystitis-osteopoikilosis syndrome,Osteopoikilosis,Buschke-Ollendorff syndrome)

Tissue-level consequences: Osteopoikilosis lesions represent focal osteosclerosis (radiographically small, discrete sclerotic foci) and have been described as reflecting a defective endochondral bone maturation process with characteristic radiographic distribution. (mortier2014traumaticfracturein pages 1-2)

How dacryocystitis fits (hypothesis from primary syndrome report): The 1993 syndrome report proposed that the necessary prerequisite for dacryocystitis is stenosis of the lacrimal sac/canal, and suggested that such stenosis may arise in the context of osteopoikilosis-associated stenosing connective tissue abnormalities. (gunal1993dacryocystitisassociatedwith pages 3-3)

1.2 Dysregulated pathways

TGF-β/BMP–SMAD signaling antagonism by LEMD3/MAN1: In the landmark genetic study, the LEMD3 C-terminus was shown to interact with SMAD MH2 domains (e.g., Smad1 for BMP and Smad2 for TGF-β), and LEMD3 overexpression suppressed BMP- and TGF-β–responsive reporter and transcriptional readouts, supporting LEMD3 as a negative regulator (antagonist) of both BMP and TGF-β/SMAD signaling. (hellemans2004lossoffunctionmutationsin pages 3-4, hellemans2004lossoffunctionmutationsin pages 1-2)

Downstream functional effects relevant to bone: A 2024 authoritative review of bone biology emphasizes that BMPs promote osteogenesis, while TGF-β functions are stage-dependent in osteoblast/chondrocyte lineage progression and skeletal homeostasis; regulatory machinery includes cytoplasmic and nuclear control of SMAD signaling. This contextualizes why disinhibition of these pathways (via reduced LEMD3 antagonism) plausibly perturbs bone patterning/remodeling. (wu2024therolesand)

Note: The Wu et al. review was retrieved but not processed into a citable evidence snippet ID by the evidence tool in the current run; therefore, it is not cited further here to avoid unsupported claims.

1.3 Cellular processes affected

From the mechanistic and clinical literature, the most defensible disrupted processes include: - SMAD signal transduction regulation (loss of antagonism → increased signaling output). (hellemans2004lossoffunctionmutationsin pages 3-4) - Bone formation / endochondral ossification maturation abnormalities (osteopoikilosis described as defective endochondral maturation). (mortier2014traumaticfracturein pages 1-2) - Fibroproliferative/stenosing lesion tendency as a putative shared process across osteopoikilosis-associated “stenosing lesions” (hypothesis). (kaparov2011dequervain’ssyndrome pages 4-4, gunal1993dacryocystitisassociatedwith pages 3-3)

2. Key molecular players

2.1 Genes/proteins

Causal gene (core): - LEMD3 (HGNC symbol: LEMD3; protein: MAN1) — inner nuclear membrane protein, binds receptor-regulated SMADs, antagonizes TGF-β/BMP signaling. (hellemans2004lossoffunctionmutationsin pages 3-4, mortier2014traumaticfracturein pages 2-3)

Variant spectrum (examples): - Whole-gene deletion and multiple truncating variants (frameshift, nonsense, splice) were reported in affected families, consistent with loss-of-function and haploinsufficiency/truncation removing the SMAD-interacting C-terminus. (hellemans2004lossoffunctionmutationsin pages 3-4, hellemans2004lossoffunctionmutationsin pages 1-2) - Additional families show segregating nonsense variants and the absence of the variant in large control sets (e.g., 342 controls), supporting pathogenicity. (couto2007anovellemd3 pages 1-3)

Evidence gap for the specific syndrome label: Open Targets currently lists no curated gene target for “dacryocystitis–osteopoikilosis syndrome” even though it links LEMD3 to osteopoikilosis (and related entries), indicating that the lacrimal phenotype is not yet integrated into some gene–disease curation pipelines. (OpenTargets Search: Dacryocystitis-osteopoikilosis syndrome,Osteopoikilosis,Buschke-Ollendorff syndrome)

2.2 Chemical entities (metabolites/drugs/small molecules)

No disease-specific metabolite or drug mechanism is established for the syndrome in the retrieved evidence. Clinical care is therefore symptom- and complication-directed (e.g., pain control in symptomatic osteopoikilosis; standard ophthalmologic management for nasolacrimal obstruction/infection).

2.3 Cell types primarily affected (inferred from mechanism)

• Osteoblast lineage / bone-forming mesenchymal cells — implicated by bone sclerosis phenotype and BMP/TGF-β roles in osteogenesis. (hellemans2004lossoffunctionmutationsin pages 3-4, mortier2014traumaticfracturein pages 1-2)
• Fibroblasts — implicated both by (i) enhanced TGF-β signaling in fibroblast context reported in the LEMD3 LOF study and (ii) hypothesis of fibroblast-driven fibroproliferation/stenosis in associated lesions. (hellemans2004lossoffunctionmutationsin pages 3-4, kaparov2011dequervain’ssyndrome pages 4-4)

2.4 Anatomical locations

• Skeleton (multiple bones; periarticular regions): radiographic lesions in phalanges, carpus, metacarpals, radius/ulna reported in the syndrome pedigree. (gunal1993dacryocystitisassociatedwith pages 1-3)
• Lacrimal drainage system: lacrimal sac/canal stenosis proposed as prerequisite for chronic dacryocystitis in the syndrome. (gunal1993dacryocystitisassociatedwith pages 3-3)

3. Biological processes disrupted (GO-oriented)

Below are ontology-ready candidate processes consistent with the cited evidence (mechanistic and clinical), suitable for GO annotation in a knowledge base:

• Regulation of BMP signaling pathway (LEMD3 antagonizes BMP-SMAD signaling). (hellemans2004lossoffunctionmutationsin pages 3-4)
• Regulation of TGF-β receptor signaling pathway (LEMD3 antagonizes TGF-β/activin SMAD signaling). (hellemans2004lossoffunctionmutationsin pages 3-4, couto2007anovellemd3 pages 4-4)
• SMAD protein signal transduction / negative regulation of SMAD signaling (direct SMAD binding and pathway antagonism). (hellemans2004lossoffunctionmutationsin pages 3-4)
• Endochondral ossification / bone maturation (osteopoikilosis described as defective endochondral maturation). (mortier2014traumaticfracturein pages 1-2)
• Fibroblast proliferation / extracellular matrix organization / tissue stenosis (hypothesis) to connect “stenosing lesions” (e.g., lacrimal stenosis; other fibroproliferative lesions) with shared pathophysiology. (kaparov2011dequervain’ssyndrome pages 4-4, gunal1993dacryocystitisassociatedwith pages 3-3)

4. Cellular components (GO-CC oriented)

• Inner nuclear membrane (LEMD3/MAN1 localization). (hellemans2004lossoffunctionmutationsin pages 3-4, couto2007anovellemd3 pages 4-4)
• Nuclear envelope (broader compartment consistent with inner nuclear membrane proteins). (hellemans2004lossoffunctionmutationsin pages 3-4)
• SMAD protein complexes / nucleus (functional interaction site for SMAD-mediated transcriptional regulation; supported by LEMD3–SMAD interaction and effects on transcriptional reporters). (hellemans2004lossoffunctionmutationsin pages 3-4)

5. Disease progression model (sequence of events)

5.1 Initiation and early molecular events

1. Germline heterozygous LEMD3 loss-of-function → reduced functional MAN1 at the inner nuclear membrane. (hellemans2004lossoffunctionmutationsin pages 3-4, OpenTargets Search: Dacryocystitis-osteopoikilosis syndrome,Osteopoikilosis,Buschke-Ollendorff syndrome)
2. Reduced antagonism of receptor-activated SMADs → increased effective output of BMP and/or TGF-β signaling programs in responsive cells. (hellemans2004lossoffunctionmutationsin pages 3-4)

5.2 Tissue remodeling and lesion development

1. In bone, altered morphogen signaling plausibly skews osteoblast/chondrocyte programs and remodeling, producing focal sclerotic bone islands typical of osteopoikilosis; clinically often incidental but can be associated with pain/effusions. (mortier2014traumaticfracturein pages 1-2)
2. In soft tissues, a subset of individuals may manifest stenosing/fibroproliferative changes (hypothesis) in anatomic conduits, including the nasolacrimal system. (kaparov2011dequervain’ssyndrome pages 4-4, gunal1993dacryocystitisassociatedwith pages 3-3)

5.3 Clinical manifestation

1. Nasolacrimal obstruction/stenosis predisposes to stasis and infection/inflammation, manifesting as chronic dacryocystitis. The syndrome report explicitly frames lacrimal stenosis as the prerequisite event. (gunal1993dacryocystitisassociatedwith pages 3-3)

6. Phenotypic manifestations and mechanistic links

6.1 Key phenotypes

• Osteopoikilosis: multiple small, symmetric periarticular sclerotic lesions; may be asymptomatic and incidental. (mortier2014traumaticfracturein pages 1-2)
• Chronic dacryocystitis: confirmed in the original family by lacrimal lavage/dacryocystography. (gunal1993dacryocystitisassociatedwith pages 1-3)

6.2 Mechanistic link between bone and lacrimal disease (strength of evidence)

• Strong evidence for bone/connective tissue molecular mechanism: LEMD3 LOF → disinhibited BMP/TGF-β–SMAD signaling (primary mechanistic evidence). (hellemans2004lossoffunctionmutationsin pages 3-4)
• Moderate evidence for lacrimal mechanism (clinical/hypothesis): lacrimal stenosis as prerequisite for dacryocystitis; “stenosing lesions” concept across osteopoikilosis-associated conditions (hypothesis). (gunal1993dacryocystitisassociatedwith pages 3-3, kaparov2011dequervain’ssyndrome pages 4-4)
• Gap: No retrieved study directly assays LEMD3/TGF-β/BMP-SMAD signaling in lacrimal sac epithelium/stroma in affected patients; therefore, the lacrimal connection remains primarily anatomical/clinical and hypothesis-driven based on stenosis biology.

7. Recent developments (priority 2023–2024)

7.1 2024 clinical updates (real-world implementations)

Recent case literature continues to treat osteopoikilosis primarily as a benign radiographic diagnosis where the main clinical “implementation” is avoiding misdiagnosis (e.g., metastatic disease) and managing symptoms conservatively; these papers often reiterate LEMD3 as the likely causal gene but typically do not add new mechanistic tissue-level work. (alghamdi2024ararecase pages 4-5)

7.2 2023–2024 knowledge gaps specific to the syndrome

No 2023–2024 publications were retrieved here that (i) re-define the dacryocystitis–osteopoikilosis syndrome at the molecular level, (ii) provide lacrimal tissue functional work, or (iii) establish genotype–phenotype correlations explaining why only a minority develop dacryocystitis.

8. Statistics and data

• Syndrome case count (primary pedigree): 5 affected members with chronic dacryocystitis and osteopoikilosis in the original report. (gunal1993dacryocystitisassociatedwith pages 1-3)
• BOS epidemiology (related disorder; contextual): In a systematic review/case series of BOS, estimated incidence 1 in 20,000, and among compiled cases, family history 92%; phenotypic distribution included skin-only 24%, bone-only 20%, and both 54%. (pope2016buschke–ollendorffsyndromea pages 1-2)

Note: These BOS statistics provide context for the LEMD3-related spectrum; they should not be directly interpreted as prevalence of dacryocystitis–osteopoikilosis syndrome.

9. Expert opinions and authoritative interpretations (from the cited literature)

• The original syndrome authors highlight a mechanistic prerequisite: “The essential prerequisite for dacryocystitis is the stenosis of the lacrimal sac or canal”, framing the lacrimal phenotype as obstruction-driven rather than primary infection. (gunal1993dacryocystitisassociatedwith pages 3-3)
• A rheumatology review case discussion suggests a unifying theme that osteopoikilosis-associated lesions show “stenosing lesions” patterns and links dacryocystitis risk to lacrimal sac stenosis, proposing shared fibroproliferative mechanisms (hypothesis). (kaparov2011dequervain’ssyndrome pages 4-4)
• The landmark genetics study provides the mechanistic anchor: LEMD3/MAN1 functions as an inner nuclear membrane antagonist of BMP and TGF-β/SMAD signaling and LOF mutations underlie osteopoikilosis/BOS. (hellemans2004lossoffunctionmutationsin pages 3-4)

10. Knowledge-base ready annotation blocks

10.1 Pathophysiology description (concise)

Dacryocystitis–osteopoikilosis syndrome is a dominantly inherited phenotype combining osteopoikilosis with chronic dacryocystitis. Osteopoikilosis is best explained by monoallelic loss-of-function in LEMD3 (MAN1), an inner nuclear membrane SMAD-binding protein that antagonizes BMP and TGF-β/activin signaling; reduced MAN1 activity increases SMAD signaling output and perturbs bone maturation/remodeling, producing focal osteosclerotic lesions. The dacryocystitis component is proposed to arise secondarily from stenosis of the lacrimal drainage system, potentially reflecting a shared propensity for stenosing/fibroproliferative connective tissue lesions in the osteopoikilosis spectrum, but direct lacrimal tissue mechanistic validation is lacking. (hellemans2004lossoffunctionmutationsin pages 3-4, mortier2014traumaticfracturein pages 1-2, gunal1993dacryocystitisassociatedwith pages 3-3, kaparov2011dequervain’ssyndrome pages 4-4)

10.2 Gene/protein annotations

• HGNC: LEMD3 (MAN1)
• Molecular function / pathway (annotation-ready): negative regulation of BMP signaling; negative regulation of TGF-β receptor signaling; SMAD binding. (hellemans2004lossoffunctionmutationsin pages 3-4)

10.3 Phenotype associations (HPO-oriented; candidate terms)

• Osteopoikilosis / osteosclerosis (radiographic sclerotic bone lesions). (mortier2014traumaticfracturein pages 1-2, gunal1993dacryocystitisassociatedwith pages 1-3)
• Dacryocystitis (chronic). (gunal1993dacryocystitisassociatedwith pages 1-3)
• Nasolacrimal duct/lacrimal sac stenosis or obstruction (as prerequisite mechanism; may map to lacrimal drainage obstruction terms). (gunal1993dacryocystitisassociatedwith pages 3-3)

10.4 Cell type involvement (CL-oriented; candidates)

• Osteoblast / osteoprogenitor cell (bone sclerosis phenotype; BMP/TGF-β relevance). (hellemans2004lossoffunctionmutationsin pages 3-4)
• Fibroblast (enhanced TGF-β signaling in fibroblasts reported; fibroproliferation hypothesis). (hellemans2004lossoffunctionmutationsin pages 3-4, kaparov2011dequervain’ssyndrome pages 4-4)

10.5 Anatomical locations (UBERON-oriented; candidates)

• Bone (multiple; periarticular regions) (gunal1993dacryocystitisassociatedwith pages 1-3)
• Lacrimal sac / nasolacrimal duct (gunal1993dacryocystitisassociatedwith pages 3-3)

10.6 Chemical entities (ChEBI-oriented)

No syndrome-specific small-molecule entities are established in the retrieved mechanistic literature.

11. Evidence items with PMIDs (where available in retrieved evidence)

• LEMD3 genetic association evidence includes literature identifiers such as PMID: 15489854 referenced by Open Targets for osteopoikilosis (corresponding to the landmark 2004 Nature Genetics paper), and additional PMIDs listed in the same Open Targets evidence bundle. (OpenTargets Search: Dacryocystitis-osteopoikilosis syndrome,Osteopoikilosis,Buschke-Ollendorff syndrome)

Note: The full PMID list for each paper was not uniformly extracted into the evidence snippets in this run; for operational knowledge-base ingestion, cross-referencing each DOI to PubMed will yield canonical PMIDs.

12. Limitations and future directions

• Direct molecular confirmation for the dacryocystitis-osteopoikilosis syndromic label (i.e., sequencing LEMD3 in confirmed lacrimal+OPK pedigrees and functional assays in lacrimal tissues) remains an unmet need in the retrieved corpus. (OpenTargets Search: Dacryocystitis-osteopoikilosis syndrome,Osteopoikilosis,Buschke-Ollendorff syndrome, gunal1993dacryocystitisassociatedwith pages 1-3)
• Mechanistic bridging studies are needed to test whether MAN1/LEMD3 loss alters fibrosis/stenosis programs in nasolacrimal tissues (e.g., fibroblast activation, ECM deposition), which is currently supported mainly by clinical reasoning and analogy to other stenosing lesions. (kaparov2011dequervain’ssyndrome pages 4-4, gunal1993dacryocystitisassociatedwith pages 3-3)

References

1. (OpenTargets Search: Dacryocystitis-osteopoikilosis syndrome,Osteopoikilosis,Buschke-Ollendorff syndrome): Open Targets Query (Dacryocystitis-osteopoikilosis syndrome,Osteopoikilosis,Buschke-Ollendorff syndrome, 3 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

2. (gunal1993dacryocystitisassociatedwith pages 1-3): I. Günal, S. Seber, N. Basaran, S. Artan, K. Günal, and E. Gokturk. Dacryocystitis associated with osteopoikilosis. Clinical Genetics, 44:211-213, Oct 1993. URL: https://doi.org/10.1111/j.1399-0004.1993.tb03882.x, doi:10.1111/j.1399-0004.1993.tb03882.x. This article has 47 citations and is from a peer-reviewed journal.

3. (hellemans2004lossoffunctionmutationsin pages 3-4): Jan Hellemans, Olena Preobrazhenska, Andy Willaert, Philippe Debeer, Peter C M Verdonk, Teresa Costa, Katrien Janssens, Bjorn Menten, Nadine Van Roy, Stefan J T Vermeulen, Ravi Savarirayan, Wim Van Hul, Filip Vanhoenacker, Danny Huylebroeck, Anne De Paepe, Jean-Marie Naeyaert, Jo Vandesompele, Frank Speleman, Kristin Verschueren, Paul J Coucke, and Geert R Mortier. Loss-of-function mutations in lemd3 result in osteopoikilosis, buschke-ollendorff syndrome and melorheostosis. Nature Genetics, 36:1213-1218, Oct 2004. URL: https://doi.org/10.1038/ng1453, doi:10.1038/ng1453. This article has 567 citations and is from a highest quality peer-reviewed journal.

4. (gunal1993dacryocystitisassociatedwith pages 3-3): I. Günal, S. Seber, N. Basaran, S. Artan, K. Günal, and E. Gokturk. Dacryocystitis associated with osteopoikilosis. Clinical Genetics, 44:211-213, Oct 1993. URL: https://doi.org/10.1111/j.1399-0004.1993.tb03882.x, doi:10.1111/j.1399-0004.1993.tb03882.x. This article has 47 citations and is from a peer-reviewed journal.

5. (hellemans2004lossoffunctionmutationsin pages 1-2): Jan Hellemans, Olena Preobrazhenska, Andy Willaert, Philippe Debeer, Peter C M Verdonk, Teresa Costa, Katrien Janssens, Bjorn Menten, Nadine Van Roy, Stefan J T Vermeulen, Ravi Savarirayan, Wim Van Hul, Filip Vanhoenacker, Danny Huylebroeck, Anne De Paepe, Jean-Marie Naeyaert, Jo Vandesompele, Frank Speleman, Kristin Verschueren, Paul J Coucke, and Geert R Mortier. Loss-of-function mutations in lemd3 result in osteopoikilosis, buschke-ollendorff syndrome and melorheostosis. Nature Genetics, 36:1213-1218, Oct 2004. URL: https://doi.org/10.1038/ng1453, doi:10.1038/ng1453. This article has 567 citations and is from a highest quality peer-reviewed journal.

6. (mumm2007deactivatinggermlinemutations pages 1-2): Steven Mumm, Deborah Wenkert, Xiafang Zhang, William H McAlister, Richard J Mier, and Michael P Whyte. Deactivating germline mutations in lemd3 cause osteopoikilosis and buschke-ollendorff syndrome, but not sporadic melorheostosis. Journal of Bone and Mineral Research, 22:243-250, Feb 2007. URL: https://doi.org/10.1359/jbmr.061102, doi:10.1359/jbmr.061102. This article has 107 citations and is from a highest quality peer-reviewed journal.

7. (couto2007anovellemd3 pages 1-3): Ana R. Couto, Jacome Bruges-Armas, Chris A. Peach, Kay Chapman, Matthew A. Brown, B. Paul Wordsworth, and Yun Zhang. A novel lemd3 mutation common to patients with osteopoikilosis with and without melorheostosis. Calcified Tissue International, 81:81-84, Jul 2007. URL: https://doi.org/10.1007/s00223-007-9043-z, doi:10.1007/s00223-007-9043-z. This article has 59 citations and is from a peer-reviewed journal.

8. (couto2007anovellemd3 pages 4-4): Ana R. Couto, Jacome Bruges-Armas, Chris A. Peach, Kay Chapman, Matthew A. Brown, B. Paul Wordsworth, and Yun Zhang. A novel lemd3 mutation common to patients with osteopoikilosis with and without melorheostosis. Calcified Tissue International, 81:81-84, Jul 2007. URL: https://doi.org/10.1007/s00223-007-9043-z, doi:10.1007/s00223-007-9043-z. This article has 59 citations and is from a peer-reviewed journal.

9. (pope2016buschke–ollendorffsyndromea pages 1-2): V. Pope, L. Dupuis, P. Kannu, R. Mendoza-Londono, D. Sajic, J. So, G. Yoon, and I. Lara‐Corrales. Buschke–ollendorff syndrome: a novel case series and systematic review. British Journal of Dermatology, 174:723-729, Apr 2016. URL: https://doi.org/10.1111/bjd.14366, doi:10.1111/bjd.14366. This article has 52 citations and is from a highest quality peer-reviewed journal.

10. (mortier2014traumaticfracturein pages 2-3): Adeline Du Mortier and Pierre-Louis Docquier. Traumatic fracture in a patient with osteopoikilosis. Case Reports in Orthopedics, 2014:1-4, Jan 2014. URL: https://doi.org/10.1155/2014/520651, doi:10.1155/2014/520651. This article has 1 citations.

11. (mortier2014traumaticfracturein pages 1-2): Adeline Du Mortier and Pierre-Louis Docquier. Traumatic fracture in a patient with osteopoikilosis. Case Reports in Orthopedics, 2014:1-4, Jan 2014. URL: https://doi.org/10.1155/2014/520651, doi:10.1155/2014/520651. This article has 1 citations.

12. (kaparov2011dequervain’ssyndrome pages 4-4): Asylbek Kaparov, Murat Uludag, Hidayet Sari, and Ülkü Akarirmak. De quervain’s syndrome associated with osteopoikilosis: a case report and review of the literature. Rheumatology International, 31:809-813, Jun 2011. URL: https://doi.org/10.1007/s00296-009-1239-2, doi:10.1007/s00296-009-1239-2. This article has 11 citations and is from a peer-reviewed journal.

13. (steensel2008buschkeollendorfsyndromereport pages 1-2): Maurice A.M. van Steensel, Michel van Geel, Valerie L.R.M. Verstraeten, and G.P. H. Lucker. Buschke-ollendorf syndrome: report of a case and a brief molecular overview. The Open Dermatology Journal, 2:5-8, Jan 2008. URL: https://doi.org/10.2174/1874372200802010005, doi:10.2174/1874372200802010005. This article has 0 citations.

14. (alghamdi2024ararecase pages 4-5): Bandar A Alghamdi. A rare case of hereditary bone dysplasia: osteopoikilosis in a mother and her son. Cureus, Jun 2024. URL: https://doi.org/10.7759/cureus.61477, doi:10.7759/cureus.61477. This article has 2 citations.