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: Opsismodysplasia
• MONDO ID: (if available)
• Category: Mendelian

Research Objectives

Please provide a comprehensive research report on the pathophysiology of Opsismodysplasia. 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

Comprehensive Research Report: Opsismodysplasia (OPSMD)

0. Disease identifiers and overview

Opsismodysplasia is a rare Mendelian skeletal dysplasia characterized by delayed skeletal maturation and severe abnormalities of endochondral bone growth. An authoritative recent review describes opsismodysplasia as a skeletal dysplasia “primarily characterized by the delayed ossification of maturing bones.” (muller2024thefunctionalroles pages 14-15)

• MONDO disease ID: MONDO:0009785 (Open Targets disease entity; retrieved via Open Targets association for OPSMD–INPPL1). (below2013wholegenomeanalysisreveals pages 5-7)
• Inheritance: Autosomal recessive (biallelic pathogenic variants). (below2013wholegenomeanalysisreveals pages 5-7, celine2013exomesequencingidentifies pages 1-2)
• Primary causal gene: INPPL1 (HGNC:6091), encoding SHIP2 (Src homology 2 domain-containing inositol 5-phosphatase 2). (below2013wholegenomeanalysisreveals pages 5-7, celine2013exomesequencingidentifies pages 1-2)

1. Key concepts and definitions (current understanding)

1.1 Core molecular definition

INPPL1/SHIP2 is a phosphoinositide 5-phosphatase that acts within the PI3K signaling network by turning over phosphatidylinositol lipids. One report summarizes SHIP2 as dephosphorylating the “lipid second messenger phosphoinositol (3,4,5)P3,” consistent with its canonical role in terminating or reshaping PI3K signaling outputs. (feist2016novelcompoundheterozygous pages 3-4)

In the discovery-era clinical genetics literature, INPPL1 is placed in the PI3K lipid-signaling axis: PI3K produces PtdIns(3,4,5)P3, which can be converted by 5-phosphatases (including SHIP2) to PtdIns(3,4)P2. (celine2013exomesequencingidentifies pages 4-4)

1.2 Pathophysiologic definition at the tissue level

Opsismodysplasia is best conceptualized as a disorder of growth plate architecture and endochondral ossification.

Growth plate histopathology in opsismodysplasia demonstrates: - Loss of normal proliferative-zone organization (columnar arrangement) - Reduction of the hypertrophic zone and fewer hypertrophic chondrocytes

These features were explicitly reported in the initial AJHG cohort, indicating that the molecular defect produces a characteristic cellular disorganization of the growth plate that plausibly explains delayed epiphyseal ossification and skeletal shortening. (celine2013exomesequencingidentifies pages 1-2)

2. Core pathophysiology

2.1 Primary mechanisms

Primary pathophysiological mechanism: biallelic INPPL1 loss-of-function (or destabilizing) variants lead to dysregulated phosphoinositide metabolism and signaling, producing growth plate disorganization, impaired chondrocyte maturation, and delayed endochondral ossification.

Evidence supporting a loss-of-function mechanism includes mutation spectrum and protein loss: - In one AJHG series, most variants were truncating or splice-site, with missense variants clustering in the catalytic 5-phosphatase domain, consistent with disrupted enzymatic function. (celine2013exomesequencingidentifies pages 4-4, celine2013exomesequencingidentifies pages 1-2) - A fetal opsismodysplasia family showed no detectable SHIP2 protein in affected amniocytes, providing direct protein-level support for functional loss. (feist2016novelcompoundheterozygous pages 3-4, feist2016novelcompoundheterozygous media 56a554cb)

2.2 Dysregulated pathways

(a) Phosphoinositide metabolism / PI3K signaling - INPPL1/SHIP2 regulates PIP species (e.g., turnover of PtdIns(3,4,5)P3 and production of PtdIns(3,4)P2), which are second messengers organizing signaling and membrane–cytoskeleton processes. (celine2013exomesequencingidentifies pages 4-4, feist2016novelcompoundheterozygous pages 3-4) - A 2024 review provides functional context: SHIP2 activation reduces plasma membrane PtdIns(3,4,5)P3 and thereby inhibits AKT signaling, supporting a mechanistic link to PI3K–AKT output modulation. (muller2024thefunctionalroles pages 14-15)

(b) PI(3,4)P2-centered signaling as a mechanistic emphasis A mechanistic review highlighted that phenotypes in catalytically inactive SHIP2 models were attributed more to the lack of PI(3,4)P2 than to simplistic “hyperactive PI3K–Akt signaling,” suggesting that loss of specific phosphoinositide species (and their binding partners) may be central to developmental phenotypes. (edimo2014ship2signalingin pages 3-5)

(c) Developmental growth-factor signaling (FGF) connections (model-organism evidence) Zebrafish Ship2 knockdown perturbs outputs of FGF signaling (reported as dorsal fate expansion in early embryogenesis), supporting the plausibility that SHIP2-dependent phosphoinositide changes can rewire growth-factor pathway responses during development. (celine2013exomesequencingidentifies pages 4-6, edimo2014ship2signalingin pages 3-5)

2.3 Cellular processes affected

Key cellular processes implicated by human pathology and SHIP2 biology include: - Chondrocyte proliferation/organization (loss of columnar organization in proliferative zone) (feist2016novelcompoundheterozygous pages 3-4, celine2013exomesequencingidentifies pages 1-2) - Chondrocyte hypertrophy/differentiation (reduced hypertrophic zone, fewer hypertrophic chondrocytes) (celine2013exomesequencingidentifies pages 1-2) - Cell expansion/size regulation and tissue mechanics (recent zebrafish evidence—see below) (voigt2024aconservedregulation pages 1-3)

3. Key molecular players

3.1 Genes/proteins

• INPPL1 (SHIP2) is the established causal gene/protein. (below2013wholegenomeanalysisreveals pages 5-7, celine2013exomesequencingidentifies pages 1-2)
• Reported disease-associated SHIP2 variants listed in a 2024 review include R401W, P659S, W688C, F722I (illustrating variant distribution beyond truncations). (muller2024thefunctionalroles pages 14-15)

Statistics (genetic contribution): In a cohort analyzed by whole-genome methods, INPPL1 mutations explained 7/12 kindreds (58%) and 5/10 simplex cases (50%), supporting genetic heterogeneity but also highlighting INPPL1 as a major contributor among clinically diagnosed cases. (below2013wholegenomeanalysisreveals pages 5-7)

3.2 Chemical entities (metabolites and small molecules)

Endogenous phosphoinositides - Phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3)—substrate/regulated lipid messenger in SHIP2 pathway context. (celine2013exomesequencingidentifies pages 4-4, feist2016novelcompoundheterozygous pages 3-4) - Phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2)—product emphasized as mechanistically important in SHIP2-deficiency phenotypes. (edimo2014ship2signalingin pages 3-5)

Research/therapeutic probes (not established OPSMD therapies) A 2024 review describes SHIP2-selective inhibition (AS1949490) as increasing insulin-induced AKT phosphorylation and improving glycemic phenotypes in diabetic mouse models, reflecting active translational pharmacology around SHIP2. These compounds are best viewed as mechanistic tools and potential future repurposing leads rather than current opsismodysplasia therapies. (muller2024thefunctionalroles pages 14-15)

3.3 Cell types

The disease-relevant cell types are growth plate chondrocytes: - Proliferative chondrocytes (loss of columnar arrangement) (feist2016novelcompoundheterozygous pages 3-4, celine2013exomesequencingidentifies pages 1-2) - Hypertrophic chondrocytes (reduced hypertrophic zone) (celine2013exomesequencingidentifies pages 1-2)

3.4 Anatomical locations / tissues

Primary tissues involved: - Growth plate cartilage (histologic disorganization) (feist2016novelcompoundheterozygous pages 3-4, celine2013exomesequencingidentifies pages 1-2) - Epiphyses (delayed ossification), vertebrae (platyspondyly), pelvis/acetabulum, long bones (radiographic manifestations) (below2013wholegenomeanalysisreveals pages 5-7, li2014opsismodysplasiaresultingfrom pages 1-3)

4. Biological processes disrupted (GO-oriented)

Evidence-supported GO-relevant processes include: - Endochondral ossification (delayed epiphyseal ossification; growth plate disruption) (celine2013exomesequencingidentifies pages 1-2, muller2024thefunctionalroles pages 14-15) - Chondrocyte differentiation and hypertrophy (reduced hypertrophic zone) (celine2013exomesequencingidentifies pages 1-2) - Chondrocyte proliferation/organization (disorganized proliferative zone; absent columnar organization) (feist2016novelcompoundheterozygous pages 3-4, celine2013exomesequencingidentifies pages 1-2) - Phosphoinositide metabolic process / phosphatidylinositol dephosphorylation (SHIP2 enzymatic function; mutation localization to catalytic domain) (celine2013exomesequencingidentifies pages 4-4, edimo2014ship2signalingin pages 3-5) - Regulation of AKT signaling (SHIP2 reduces membrane PIP3 and inhibits AKT signaling in reviewed contexts) (muller2024thefunctionalroles pages 14-15) - FGF signaling modulation (zebrafish knockdown evidence) (edimo2014ship2signalingin pages 3-5)

5. Cellular components (where key processes occur)

Opsismodysplasia mechanisms localize to compartments where SHIP2 acts on phosphoinositides: - Plasma membrane: phosphoinositide substrates and PI3K signaling lipids (PIP3/PIP2) are membrane-associated; SHIP2 activity affects membrane PIP3 and AKT signaling output. (muller2024thefunctionalroles pages 14-15) - Cytosolic signaling complexes / docking interactions: INPPL1 has described non-catalytic scaffold/docking roles interacting with cytoskeletal and receptor-associated proteins, potentially relevant to organized growth plate column formation. (celine2013exomesequencingidentifies pages 4-6)

6. Disease progression model (sequence from trigger to phenotype)

1. Initiating trigger: Biallelic pathogenic variants in INPPL1 (often truncating/splice or catalytic missense) produce SHIP2 loss or dysfunction. (below2013wholegenomeanalysisreveals pages 5-7, celine2013exomesequencingidentifies pages 1-2)
2. Molecular consequence: Impaired phosphoinositide turnover (PtdIns(3,4,5)P3 → PtdIns(3,4)P2) and altered downstream signaling outputs (including PI3K–AKT modulation and potentially growth factor pathways such as FGF, per zebrafish data). (celine2013exomesequencingidentifies pages 4-4, edimo2014ship2signalingin pages 3-5)
3. Cellular consequence in growth plate: Proliferative chondrocytes lose normal columnar organization; hypertrophic zone is reduced with fewer hypertrophic chondrocytes. (celine2013exomesequencingidentifies pages 1-2)
4. Tissue consequence: Impaired endochondral ossification manifests as delayed epiphyseal ossification and poor mineralization with characteristic skeletal radiology (e.g., platyspondyly). (below2013wholegenomeanalysisreveals pages 5-7, li2014opsismodysplasiaresultingfrom pages 1-3)
5. Organism-level outcomes: Severe short stature/micromelia; spinal deformity (scoliosis); thoracic restriction can contribute to pulmonary hypoplasia/respiratory insufficiency in severe cases. (celine2013exomesequencingidentifies pages 4-4)

Recent in vivo reinforcement (2024): Zebrafish inppl1a mutants are shorter from early larval stages and later develop notochord/spine abnormalities (thoracic scoliosis, vertebral malformations), supporting a conserved role in axial growth and endochondral lengthening. (voigt2024aconservedregulation pages 1-3)

7. Phenotypic manifestations (HP-oriented) and mechanistic links

Key clinical/radiographic phenotypes include: - Severe short stature and micromelia—consistent with impaired growth plate function and endochondral bone formation. (celine2013exomesequencingidentifies pages 4-4, celine2013exomesequencingidentifies pages 1-2) - Delayed epiphyseal and carpal ossification—directly matches the disease definition and endochondral ossification defect. (muller2024thefunctionalroles pages 14-15, li2014opsismodysplasiaresultingfrom pages 1-3) - Platyspondyly and skeletal undermineralization—consistent with defective ossification/mineralization. (below2013wholegenomeanalysisreveals pages 5-7, li2014opsismodysplasiaresultingfrom pages 1-3) - Scoliosis—reported clinically and supported by zebrafish model axial curvature. (celine2013exomesequencingidentifies pages 4-4, voigt2024aconservedregulation pages 1-3) - Narrow thorax / pulmonary hypoplasia in severe prenatal/perinatal cases—likely secondary to shortened ribs/vertebral anomalies and restricted thoracic development. (celine2013exomesequencingidentifies pages 4-4) - Low bone density and renal phosphate wasting have been described in an INPPL1-mutant case, suggesting that mineral metabolism abnormalities may modify skeletal outcomes in some patients. (li2014opsismodysplasiaresultingfrom pages 1-3)

8. Recent developments and latest research (prioritizing 2023–2024)

8.1 2024 SHIP2 disease-mechanism and pharmacology synthesis

A 2024 review consolidates SHIP2’s roles across human diseases and explicitly includes opsismodysplasia as an INPPL1/SHIP2-mutation disorder defined by delayed ossification. It also connects SHIP2 enzymology to AKT signaling modulation and summarizes pharmacologic tool compounds (e.g., AS1949490) demonstrating that SHIP2 is chemically tractable. (muller2024thefunctionalroles pages 14-15)

8.2 2024 organismal mechanism work relevant to skeletal growth

A 2024 zebrafish preprint provides new in vivo evidence that INPPL1 ortholog activity is required for cell expansion, notochord mechanics, spine morphogenesis, and endochondral bone lengthening—directly relevant to how opsismodysplasia could arise from altered cell/tissue growth mechanics in developing skeletal structures. (voigt2024aconservedregulation pages 1-3)

9. Current applications and real-world implementations

9.1 Clinical implementation: molecular diagnosis and counseling

Real-world implementation is primarily through genetic testing (exome/genome sequencing) for INPPL1 variants in suspected skeletal dysplasia cases. Early discovery work established that biallelic INPPL1 variants can be found across multiple unrelated families, supporting INPPL1 as a key diagnostic target. (celine2013exomesequencingidentifies pages 1-2)

9.2 Supportive management (example of mineral metabolism intervention)

A 2014 clinical report described renal phosphate wasting and very low bone density in an affected individual; phosphate replacement improved ambulation and dental eruption, and pamidronate was administered for low bone mineral density. This illustrates that while no disease-modifying therapy for the core signaling defect exists, targeted supportive interventions may improve function in selected patients. (li2014opsismodysplasiaresultingfrom pages 1-3)

10. Expert opinions and analysis (authoritative synthesis)

• Primary conceptual model: opsismodysplasia is a growth-plate/endocondral-ossification disorder caused by disruption of phosphoinositide signaling via SHIP2 loss-of-function. This is supported by the convergence of (i) mutation patterns that abolish catalytic function, (ii) direct protein loss in patient-derived cells, and (iii) consistent growth plate disorganization. (feist2016novelcompoundheterozygous pages 3-4, celine2013exomesequencingidentifies pages 1-2, feist2016novelcompoundheterozygous media 56a554cb)
• Mechanistic nuance: synthesis work highlights that SHIP2 biology may not reduce to “more AKT signaling”; rather, specific depletion of PI(3,4)P2 (and its effector interactions) may drive developmental phenotypes, which could explain why pathway readouts may differ across tissues and models. (edimo2014ship2signalingin pages 3-5)
• Translational interpretation: 2024 reviews show SHIP2 is chemically targetable with inhibitors developed for metabolic/neuroinflammatory indications; however, because opsismodysplasia reflects developmental skeletal patterning and growth plate architecture, any future translation would likely require careful timing and tissue targeting, and is not currently established. (muller2024thefunctionalroles pages 14-15)

11. Evidence figure (protein-level evidence)

A key experimental/clinical evidence item is an immunoblot showing absence of SHIP2 protein in proband amniocytes (with α-tubulin loading control), supporting a loss-of-protein mechanism in at least some genotypes. (feist2016novelcompoundheterozygous media 56a554cb)

12. Evidence tables for knowledge-base population

Below are curated tables intended for direct knowledge-base population.

Table: This table compiles the main mechanistic and experimental evidence linking INPPL1/SHIP2 dysfunction to opsismodysplasia, spanning discovery genetics, phosphoinositide signaling, growth-plate pathology, and recent model-organism work. It is useful as a concise evidence map for disease knowledge-base curation.

Table: This table maps core opsismodysplasia mechanisms, phenotypes, cells, tissues, and chemicals to ontology-style identifiers suitable for knowledge-base curation. It emphasizes the INPPL1/SHIP2-centered phosphoinositide signaling defect and its links to growth plate disorganization and impaired endochondral ossification.

13. Evidence items with PMIDs (primary literature prioritized)

• Below et al., AJHG (2013) Whole-genome analysis; INPPL1 mutations in 58% of kindreds and 50% of simplex cases; links to mouse developmental growth phenotypes. PMID: 23273569; DOI: 10.1016/j.ajhg.2012.11.011; Published Jan 2013. (below2013wholegenomeanalysisreveals pages 5-7)
• Huber et al., AJHG (2013) Exome sequencing; 12 INPPL1 mutations in 10 families; growth plate disorganization and reduced hypertrophic zone. DOI: 10.1016/j.ajhg.2012.11.015; Published Jan 2013. (celine2013exomesequencingidentifies pages 1-2)

Limitations of the current evidence base

Opsismodysplasia is ultra-rare; as a result, the most direct growth-plate mechanistic evidence remains concentrated in the 2013 discovery literature and a limited number of follow-up reports. Recent (2023–2024) work strengthens general SHIP2 signaling context and provides new model-organism evidence for skeletal growth roles, but cartilage-specific PI3K–AKT/FGF pathway readouts in human growth plate cells remain sparse in the accessible literature set. (edimo2014ship2signalingin pages 3-5, muller2024thefunctionalroles pages 14-15, voigt2024aconservedregulation pages 1-3)

References

1. (muller2024thefunctionalroles pages 14-15): Spike Murphy Müller and Manfred Jücker. The functional roles of the src homology 2 domain-containing inositol 5-phosphatases ship1 and ship2 in the pathogenesis of human diseases. International Journal of Molecular Sciences, 25:5254, May 2024. URL: https://doi.org/10.3390/ijms25105254, doi:10.3390/ijms25105254. This article has 16 citations.

2. (below2013wholegenomeanalysisreveals pages 5-7): Jennifer E. Below, Dawn L. Earl, Kathryn M. Shively, Margaret J. McMillin, Joshua D. Smith, Emily H. Turner, Mark J. Stephan, Lihadh I. Al-Gazali, Jozef L. Hertecant, David Chitayat, Sheila Unger, Daniel H. Cohn, Deborah Krakow, James M. Swanson, Elaine M. Faustman, Jay Shendure, Deborah A. Nickerson, and Michael J. Bamshad. Whole-genome analysis reveals that mutations in inositol polyphosphate phosphatase-like 1 cause opsismodysplasia. American journal of human genetics, 92 1:137-43, Jan 2013. URL: https://doi.org/10.1016/j.ajhg.2012.11.011, doi:10.1016/j.ajhg.2012.11.011. This article has 67 citations and is from a highest quality peer-reviewed journal.

3. (celine2013exomesequencingidentifies pages 1-2): Céline Huber, Eissa Ali Faqeih, Deborah Bartholdi, Christine Bole-Feysot, Zvi Borochowitz, Denise P Cavalcanti, Amandine Frigo, Patrick Nitschke, Joelle Roume, Heloísa G Santos, Stavit A Shalev, Andrea Superti-Furga, Anne-Lise Delezoide, Martine Le Merrer, Arnold Munnich, and Valérie Cormier-Daire. Exome sequencing identifies inppl1 mutations as a cause of opsismodysplasia. American journal of human genetics, 92 1:144-9, Jan 2013. URL: https://doi.org/10.1016/j.ajhg.2012.11.015, doi:10.1016/j.ajhg.2012.11.015. This article has 62 citations and is from a highest quality peer-reviewed journal.

4. (feist2016novelcompoundheterozygous pages 3-4): Cori Feist, Paul Holden, and Jamie Fitzgerald. Novel compound heterozygous mutations in inositol polyphosphate phosphatase-like 1 in a family with severe opsismodysplasia. Clinical Dysmorphology, 25:152–155, Oct 2016. URL: https://doi.org/10.1097/mcd.0000000000000136, doi:10.1097/mcd.0000000000000136. This article has 10 citations and is from a peer-reviewed journal.

5. (celine2013exomesequencingidentifies pages 4-4): Céline Huber, Eissa Ali Faqeih, Deborah Bartholdi, Christine Bole-Feysot, Zvi Borochowitz, Denise P Cavalcanti, Amandine Frigo, Patrick Nitschke, Joelle Roume, Heloísa G Santos, Stavit A Shalev, Andrea Superti-Furga, Anne-Lise Delezoide, Martine Le Merrer, Arnold Munnich, and Valérie Cormier-Daire. Exome sequencing identifies inppl1 mutations as a cause of opsismodysplasia. American journal of human genetics, 92 1:144-9, Jan 2013. URL: https://doi.org/10.1016/j.ajhg.2012.11.015, doi:10.1016/j.ajhg.2012.11.015. This article has 62 citations and is from a highest quality peer-reviewed journal.

6. (feist2016novelcompoundheterozygous media 56a554cb): Cori Feist, Paul Holden, and Jamie Fitzgerald. Novel compound heterozygous mutations in inositol polyphosphate phosphatase-like 1 in a family with severe opsismodysplasia. Clinical Dysmorphology, 25:152–155, Oct 2016. URL: https://doi.org/10.1097/mcd.0000000000000136, doi:10.1097/mcd.0000000000000136. This article has 10 citations and is from a peer-reviewed journal.

7. (edimo2014ship2signalingin pages 3-5): William's Elong Edimo, Stéphane Schurmans, Pierre P. Roger, and Christophe Erneux. Ship2 signaling in normal and pathological situations: its impact on cell proliferation. Advances in Biological Regulation, 54:142-151, Jan 2014. URL: https://doi.org/10.1016/j.jbior.2013.09.002, doi:10.1016/j.jbior.2013.09.002. This article has 37 citations and is from a peer-reviewed journal.

8. (celine2013exomesequencingidentifies pages 4-6): Céline Huber, Eissa Ali Faqeih, Deborah Bartholdi, Christine Bole-Feysot, Zvi Borochowitz, Denise P Cavalcanti, Amandine Frigo, Patrick Nitschke, Joelle Roume, Heloísa G Santos, Stavit A Shalev, Andrea Superti-Furga, Anne-Lise Delezoide, Martine Le Merrer, Arnold Munnich, and Valérie Cormier-Daire. Exome sequencing identifies inppl1 mutations as a cause of opsismodysplasia. American journal of human genetics, 92 1:144-9, Jan 2013. URL: https://doi.org/10.1016/j.ajhg.2012.11.015, doi:10.1016/j.ajhg.2012.11.015. This article has 62 citations and is from a highest quality peer-reviewed journal.

9. (voigt2024aconservedregulation pages 1-3): Brittney Voigt, Katherine Frazier, Donya Yazdi, Paul Gontarz, Bo Zhang, Diane S. Sepich, Lilianna Solnica-Krezel, and Ryan S. Gray. A conserved regulation of cell expansion underlies notochord mechanics, spine morphogenesis, and endochondral bone lengthening. bioRxiv, Aug 2024. URL: https://doi.org/10.1101/2024.08.12.607640, doi:10.1101/2024.08.12.607640. This article has 2 citations.

10. (li2014opsismodysplasiaresultingfrom pages 1-3): Bing Li, Deborah Krakow, Deborah A. Nickerson, Michael J. Bamshad, Yong Chang, Ralph S. Lachman, Alev Yilmaz, Hülya Kayserili, and Daniel H. Cohn. Opsismodysplasia resulting from an insertion mutation in the sh2 domain, which destabilizes inppl1. American Journal of Medical Genetics Part A, 164:2407-2411, Jun 2014. URL: https://doi.org/10.1002/ajmg.a.36640, doi:10.1002/ajmg.a.36640. This article has 19 citations.

11. (feist2016novelcompoundheterozygous pages 4-7): Cori Feist, Paul Holden, and Jamie Fitzgerald. Novel compound heterozygous mutations in inositol polyphosphate phosphatase-like 1 in a family with severe opsismodysplasia. Clinical Dysmorphology, 25:152–155, Oct 2016. URL: https://doi.org/10.1097/mcd.0000000000000136, doi:10.1097/mcd.0000000000000136. This article has 10 citations and is from a peer-reviewed journal.