ADGRG1-related Bilateral Frontoparietal Polymicrogyria (BFPP): Comprehensive Disease Characteristics Report

Target disease

Disease name: ADGRG1-related Bilateral Frontoparietal Polymicrogyria (BFPP)
Category: Mendelian (autosomal recessive)

1. Disease information

1.1 Overview (what is the disease?)

ADGRG1-related bilateral frontoparietal polymicrogyria (BFPP) is a congenital malformation of cortical development characterized by bilateral frontoparietal polymicrogyria, typically showing an anterior-to-posterior gradient of severity, and commonly accompanied by white-matter signal abnormalities plus brainstem/cerebellar hypoplasia on MRI, with neurodevelopmental disability and high rates of epilepsy and oculomotor/cerebellar signs. (piao2005genotype–phenotypeanalysisof pages 3-5, khatib2024adgrg1relatedpolymicrogyriasyndrome pages 1-3)

A core definition of polymicrogyria used in BFPP literature is: “a cortical malformation characterized by supernumerary, small gyri with abnormal cortical lamination.” (piao2005genotype–phenotypeanalysisof pages 1-2)

1.2 Key identifiers and nomenclature

Table: This table summarizes the key nomenclature and identifier anchors for ADGRG1-related bilateral frontoparietal polymicrogyria, including OMIM and MONDO mappings plus gene naming and chromosomal locus information. It is useful for harmonizing disease knowledge base entries across clinical and genomic resources.

Notes on missing identifiers: Orphanet, ICD-10/ICD-11, and MeSH identifiers specific to BFPP were not available in the retrieved full-text evidence; therefore, they are not reported here.

1.3 Synonyms / alternative names

Common disease names in the retrieved literature include: - “Bilateral frontoparietal polymicrogyria (BFPP)” (piao2005genotype–phenotypeanalysisof pages 1-2) - “ADGRG1-related polymicrogyria syndrome” (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 1-3) - “GPR56-related polymicrogyria” / “GPR56 mutations” (ADGRG1 formerly known as GPR56) (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 1-3, khatib2024adgrg1relatedpolymicrogyriasyndrome pages 6-7)

1.4 Evidence provenance

Evidence in this report is derived from aggregated disease-level resources (e.g., OpenTargets) and aggregated literature evidence (case series + reviews), supplemented by individual patient/family case reports with molecular confirmation. (OpenTargets Search: polymicrogyria,bilateral frontoparietal polymicrogyria-ADGRG1, piao2005genotype–phenotypeanalysisof pages 3-5, carneiro2021casereportdiffuse pages 1-2)

2. Etiology

2.1 Disease causal factors

Primary cause: biallelic (typically homozygous) loss-of-function or deleterious variants in ADGRG1 (GPR56) causing abnormal cortical development with characteristic MRI findings and neurodevelopmental impairment. (piao2005genotype–phenotypeanalysisof pages 3-5, piao2005genotype–phenotypeanalysisof pages 1-2, chiang2011diseaseassociatedgpr56mutations pages 1-2)

Abstract quote (primary mechanistic genetics): Chiang et al. state, “Loss-of-function mutations in the gene encoding G protein-coupled receptor 56 (GPR56) lead to bilateral frontoparietal polymicrogyria (BFPP), an autosomal recessive disorder affecting brain development.” (chiang2011diseaseassociatedgpr56mutations pages 1-2)

2.2 Risk factors

• Consanguinity is a major familial/contextual risk factor for recessive BFPP and is common among reported pedigrees. (jansen2005geneticsofthe pages 5-6, khatib2024adgrg1relatedpolymicrogyriasyndrome pages 1-3)
• Family history of BFPP / known familial ADGRG1 variant increases recurrence risk consistent with autosomal recessive inheritance. (carneiro2021casereportdiffuse pages 1-2, carneiro2021casereportdiffuse pages 2-3)

2.3 Protective factors

No genetic or environmental protective factors were identified in the retrieved evidence.

2.4 Gene–environment interactions

No specific gene–environment interaction evidence was identified in the retrieved sources.

3. Phenotypes

3.1 Core clinical phenotype spectrum and frequencies

Table: This table summarizes the core clinical and imaging phenotype spectrum reported for ADGRG1-related bilateral frontoparietal polymicrogyria, with frequencies drawn from classic and updated literature reviews. It is useful for knowledge-base curation because it aligns phenotype terms, quantitative prevalence, and suggested HPO mappings with supporting citations.

Key quantitative phenotype statistics from landmark and updated reviews include: - In a classic cohort of 29 typical BFPP cases, cerebellar signs (94%), dysconjugate gaze (88%), and seizures (95%) were highly prevalent; cognitive and motor developmental delay were universal. (piao2005genotype–phenotypeanalysisof pages 3-5) - In an updated literature synthesis (as captured in the Carneiro 2021 excerpts), seizures were reported in 88.2%, with 60.0% of those being drug-refractory; severe cognitive impairment was reported in 79.3%; oculomotor findings in 92.1%. (carneiro2021casereportdiffuse pages 5-6, carneiro2021casereportdiffuse pages 3-5) - In the Khatib 2024 review excerpt, seizures were present in 75/83 (90.4%), refractory in 41/75 (54.7%). (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 6-7)

3.2 Phenotype characteristics (onset, progression, QoL impact)

• Onset: Congenital/infantile, with developmental delay/hypotonia often evident within the first year; seizures typically begin in infancy or childhood. (carneiro2021casereportdiffuse pages 2-3, parrini2009bilateralfrontoparietalpolymicrogyria pages 3-5)
• Course: The malformation is structural and nonprogressive, but functional outcomes vary; epilepsy can be refractory and can contribute to developmental decompensation (epileptic encephalopathy-like course). (carneiro2021casereportdiffuse pages 3-5, parrini2009bilateralfrontoparietalpolymicrogyria pages 6-8)
• Quality-of-life impact: Severe intellectual disability, refractory epilepsy, impaired ambulation, and oculomotor dysfunction can markedly limit independence and communication; quantitative QoL metrics (e.g., EQ-5D/SF-36) were not identified in the retrieved literature.

3.3 Suggested HPO terms

HPO suggestions are included per-phenotype in Artifact-01.

4. Genetic / molecular information

4.1 Causal gene(s)

ADGRG1 (former name GPR56) is the established causal gene for classic BFPP, with autosomal recessive inheritance. (piao2005genotype–phenotypeanalysisof pages 3-5, khatib2024adgrg1relatedpolymicrogyriasyndrome pages 1-3)

4.2 Pathogenic variant spectrum

Table: This table summarizes the core human genetic evidence linking ADGRG1 (GPR56) to bilateral frontoparietal polymicrogyria, including inheritance, variant classes, representative alleles, and cohort-level statistics. It is useful for quickly mapping variant-level findings to phenotypic interpretation, population context, and evidence type.

Key genetic findings: - Landmark genotype–phenotype analysis identified homozygous GPR56 mutations in all 29 patients with typical BFPP (defining ADGRG1 as a major Mendelian cause of this imaging phenotype). (piao2005genotype–phenotypeanalysisof pages 1-2) - BFPP-associated missense variants cluster in extracellular regions (ECD/GPS/extracellular loops), with additional truncating variants and occasional regulatory variants (e.g., promoter deletion affecting expression in developing neurons). (ke2008biochemicalcharacterizationof pages 1-2, murayama2020thepolymicrogyriaassociatedgpr56 pages 1-2) - By the time of the 2021 review excerpt, ADGRG1 BFPP-spectrum variants had been reported in 77 patients from 47 pedigrees with 34 distinct variants. (carneiro2021casereportdiffuse pages 3-5)

4.3 Functional consequences

Many BFPP-associated variants cause loss-of-function via impaired receptor maturation/processing/trafficking and impaired ligand interactions (see Mechanism/Pathophysiology). (chiang2011diseaseassociatedgpr56mutations pages 3-5, chiang2011diseaseassociatedgpr56mutations pages 10-11)

4.4 Modifier genes / multilocus disease

The retrieved excerpts note that broader sequencing (exome/genome) can reveal additional pathogenic variants that may modify severity in malformation syndromes; specific validated modifier genes for ADGRG1-BFPP were not established in the retrieved excerpts. (carneiro2021casereportdiffuse pages 3-5)

4.5 Epigenetics / chromosomal abnormalities

No disease-specific epigenetic signatures or recurrent chromosomal abnormalities were identified in the retrieved evidence.

5. Environmental information

No convincing disease-specific environmental, lifestyle, or infectious etiologic triggers were identified in the retrieved evidence for ADGRG1-related BFPP as a Mendelian disorder. However, congenital infections (e.g., CMV/HSV) can mimic the MRI pattern and must be considered in differential diagnosis. (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 4-6)

6. Mechanism / pathophysiology

6.1 Molecular mechanism: ADGRG1 receptor biology and BFPP loss-of-function

ADGRG1/GPR56 is an adhesion GPCR with an extracellular domain (ECD), a GPCR proteolysis site (GPS/GAIN) and a 7TM signaling domain; BFPP-associated missense variants occur in extracellular regions and can cause disease through multiple convergent loss-of-function mechanisms. (chiang2011diseaseassociatedgpr56mutations pages 1-2)

Primary functional mechanisms in BFPP variants (cellular/biochemical): - Defective processing and trafficking: BFPP mutants frequently show ER retention, EndoH-sensitive glycosylation, reduced surface expression, and likely increased degradation. (chiang2011diseaseassociatedgpr56mutations pages 3-5, chiang2011diseaseassociatedgpr56mutations pages 5-6) - Loss of GPS proteolysis: GPS-site mutants (e.g., C346S, W349S) can become uncleaved single-chain forms and fail to reach the cell surface. (chiang2011diseaseassociatedgpr56mutations pages 3-5, ke2008biochemicalcharacterizationof pages 1-2) - Impaired ligand interactions / adhesion: N-terminal variants can abolish or reduce binding to a protein ligand and impair ligand-dependent adhesion. (chiang2011diseaseassociatedgpr56mutations pages 8-10, chiang2011diseaseassociatedgpr56mutations pages 7-8) - Membrane microdomain mislocalization: Some extracellular-loop variants (e.g., R565W, L640R) alter β-subunit behavior and lipid-raft distribution, supporting pathogenic mechanisms beyond simple surface expression loss. (chiang2011diseaseassociatedgpr56mutations pages 8-10)

6.2 Signaling pathways and ligand modalities (current understanding; 2023–2024 emphasis)

ADGRG1 signaling is strongly linked to Gα12/Gα13 → RhoA pathways: - Abstract quote (2024): “GPR56 constitutively activates both G12 and G13.” (jallouli2024gproteinselectivity pages 1-2) - Abstract quote (2024): “[10C7 antibody] led to an activation that favors G13 over G12.” (jallouli2024gproteinselectivity pages 1-2)

Endogenous ligand/binding-partner biology relevant to development and myelination includes: - Collagen III (basement membrane ligand): ADGRG1 binding to collagen III in the basement membrane is linked to Gα12/13–RhoA-dependent inhibition of neuronal migration, and loss of this regulation contributes to BFPP cortical malformation. (einspahr2022pathophysiologicalimpactof pages 5-9) - Transglutaminase-2 (TG2): TG2 is an ADGRG1 ligand/binding partner in multiple contexts, including oligodendrocyte lineage signaling (microglia→OPC) and epithelial migration systems. (giera2018microglialtransglutaminase2drives pages 1-2, giera2018microglialtransglutaminase2drives pages 3-5, bauer2024mesenchymaltransglutaminase2 pages 1-2)

Recent mechanistic development (2024, epithelial context): Bauer et al. describe TG2–GPR56 as a ligand–receptor pair that activates RhoA/ROCK and ADAM17, leading to EGFR transactivation and rapid keratinocyte migration, illustrating mechanistic routes by which extracellular ligands can drive ADGRG1 signaling. (bauer2024mesenchymaltransglutaminase2 pages 1-2, bauer2024mesenchymaltransglutaminase2 pages 2-5, bauer2024mesenchymaltransglutaminase2 pages 6-9)

6.3 Causal chain from gene defect to clinical phenotype (integrated)

1) Biallelic ADGRG1 variants → impaired receptor processing/trafficking and/or impaired extracellular ligand interactions (collagen III; protein ligands), reducing effective receptor function at the cell surface. (chiang2011diseaseassociatedgpr56mutations pages 3-5, chiang2011diseaseassociatedgpr56mutations pages 10-11, chiang2011diseaseassociatedgpr56mutations pages 1-2)
2) Reduced ADGRG1 function perturbs Gα12/13–RhoA signaling that normally regulates neuronal migration, cortical lamination, and pial basement membrane integrity. (einspahr2022pathophysiologicalimpactof pages 5-9, murayama2020thepolymicrogyriaassociatedgpr56 pages 1-2)
3) Developmental disruption yields frontoparietal-predominant polymicrogyria, abnormal cortical lamination, associated white-matter abnormalities, and posterior fossa involvement (pons/vermian/cerebellar hypoplasia), producing a characteristic radiologic pattern. (piao2005genotype–phenotypeanalysisof pages 3-5, piao2005genotype–phenotypeanalysisof media 547d7d36)
4) The resulting circuit malformation and developmental perturbations manifest as global developmental delay/intellectual disability, seizures (often refractory), oculomotor abnormalities, pyramidal signs/spasticity, and cerebellar signs. (piao2005genotype–phenotypeanalysisof pages 3-5, carneiro2021casereportdiffuse pages 5-6)

6.4 Suggested ontology terms (mechanism, anatomy, cells)

GO Biological Process (suggested): - Neuronal migration (GO:0001764) (supported conceptually by Gα12/13–RhoA migration regulation and cortical malformation) (einspahr2022pathophysiologicalimpactof pages 5-9) - Cell adhesion (GO:0007155) (ligand-dependent adhesion and receptor–ligand interactions) (chiang2011diseaseassociatedgpr56mutations pages 10-11) - Myelination / glial development (GO:0042552; oligodendrocyte precursor proliferation related processes) (giera2018microglialtransglutaminase2drives pages 1-2, ackerman2018gpr56adgrg1regulatesdevelopment pages 1-2)

Cell Ontology (CL; suggested): - Radial glial cell (CL:0000243) (pial basement membrane/endfeet abnormalities in Gpr56 loss model) (murayama2020thepolymicrogyriaassociatedgpr56 pages 1-2) - Neural progenitor cell (CL:0011020) (reduced proliferation in mouse loss models; BFPP developmental mechanism) (murayama2020thepolymicrogyriaassociatedgpr56 pages 1-2) - GABAergic interneuron (CL:0000099) (e1m promoter activity in developing GABAergic neurons; epilepsy link) (murayama2020thepolymicrogyriaassociatedgpr56 pages 1-2) - Oligodendrocyte precursor cell (CL:0002453) (TG2→ADGRG1 promotes OPC proliferation and remyelination) (giera2018microglialtransglutaminase2drives pages 1-2) - Microglial cell (CL:0000129) (microglial TG2 source) (giera2018microglialtransglutaminase2drives pages 3-5) - Schwann cell (CL:0000688) (peripheral myelin roles) (ackerman2018gpr56adgrg1regulatesdevelopment pages 1-2)

UBERON (suggested): - Cerebral cortex (UBERON:0000956), frontal lobe (UBERON:0001870), parietal lobe (UBERON:0001872) (piao2005genotype–phenotypeanalysisof pages 3-5) - Pons (UBERON:0000988), cerebellar vermis (UBERON:0002124), cerebellum (UBERON:0002037) (piao2005genotype–phenotypeanalysisof pages 3-5, piao2005genotype–phenotypeanalysisof media 547d7d36) - Cerebral white matter (UBERON:0002314) (piao2005genotype–phenotypeanalysisof pages 3-5)

7. Anatomical structures affected

7.1 Organ/system level

Primary affected system is the central nervous system, especially: - Bilateral frontoparietal cerebral cortex (polymicrogyria) (piao2005genotype–phenotypeanalysisof pages 3-5) - White matter (patchy signal change/hypomyelination) (piao2005genotype–phenotypeanalysisof pages 3-5, carneiro2021casereportdiffuse pages 2-3) - Brainstem and cerebellum (pons/vermian/cerebellar hypoplasia) (piao2005genotype–phenotypeanalysisof pages 3-5, piao2005genotype–phenotypeanalysisof media 547d7d36)

7.2 Tissue/cell level

Evidence from mammalian models indicates involvement of neurodevelopmental and glial lineages (radial glia, neuronal progenitors, migrating neurons), and later roles in myelination involving Schwann cells and oligodendrocyte lineage cells. (murayama2020thepolymicrogyriaassociatedgpr56 pages 1-2, ackerman2018gpr56adgrg1regulatesdevelopment pages 1-2, giera2018microglialtransglutaminase2drives pages 1-2)

7.3 Subcellular level

Mutant receptor biology implicates ER retention/misprocessing (EndoH sensitivity) and altered membrane microdomain distribution (lipid rafts). (chiang2011diseaseassociatedgpr56mutations pages 3-5, chiang2011diseaseassociatedgpr56mutations pages 8-10)

8. Temporal development

• Typical onset: congenital/infancy with early psychomotor delay; seizures often begin in infancy or early childhood. (carneiro2021casereportdiffuse pages 2-3, parrini2009bilateralfrontoparietalpolymicrogyria pages 3-5)
• Progression: structural malformation is static; clinical trajectory is variable and can be complicated by refractory epilepsy and developmental plateau/regression. (carneiro2021casereportdiffuse pages 3-5, carneiro2021casereportdiffuse pages 1-2)

9. Inheritance and population

9.1 Inheritance

BFPP is autosomal recessive, frequently observed in consanguineous pedigrees; classic cohorts show biallelic/homozygous ADGRG1 variants in typical BFPP. (jansen2005geneticsofthe pages 5-6, piao2005genotype–phenotypeanalysisof pages 1-2)

9.2 Epidemiology

True prevalence/incidence estimates specific to ADGRG1-related BFPP were not identified in the retrieved evidence.

9.3 Population and geographic distribution

Reported mutation-positive BFPP families in the landmark cohort included Arabic-speaking Middle Eastern, Pakistani, Indian, Afghani, Canadian, Turkish, Italian, Israeli, and Hispanic American backgrounds. (piao2005genotype–phenotypeanalysisof pages 3-5)

9.4 Statistics supporting clinical relevance in PMG cohorts (recent)

In a large polymicrogyria genetics study (275 families), a genetic etiology was found in 32.7% (90/275); ADGRG1/GPR56 was listed among known PMG genes detected in the cohort, though per-gene counts were not extractable from the retrieved excerpts. (akula2023exomesequencingand pages 2-3)

10. Diagnostics

Table: This table summarizes practical diagnostic workflows, common differential-diagnosis pitfalls, symptomatic management, and prevention/counseling strategies for ADGRG1-related bilateral frontoparietal polymicrogyria. It is useful for translating case-report and cohort evidence into a knowledge-base-ready clinical implementation view.

Key diagnostic principles: - Diagnosis is typically suspected from MRI pattern and confirmed by molecular testing (panel or WES) with segregation and ACMG-based interpretation. (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 1-3, carneiro2021casereportdiffuse pages 2-3) - Important diagnostic pitfalls include mimicry of congenital CMV/HSV and cobblestone/dystroglycanopathy-like presentations. (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 4-6, carneiro2021casereportdiffuse pages 2-3)

11. Outcome / prognosis

• Many individuals have severe intellectual disability and motor impairment; however, ambulation is achieved in a majority in aggregated series (e.g., 81.6% in one literature synthesis; 44/63 ~70% in another), indicating variable functional outcomes. (carneiro2021casereportdiffuse pages 3-5, khatib2024adgrg1relatedpolymicrogyriasyndrome pages 4-6)
• Epilepsy is common and frequently refractory (e.g., 54.7–60% refractory among seizure-affected individuals in aggregated datasets), which is a major driver of morbidity. (carneiro2021casereportdiffuse pages 5-6, khatib2024adgrg1relatedpolymicrogyriasyndrome pages 6-7)
• Disease-specific mortality rates for BFPP were not identified in the retrieved evidence; one severe multi-system twin presentation with ADGRG1 p.Arg565Trp (plus an additional variant) died before age 2, illustrating potential severity in complex/overlapping cases rather than typical BFPP prognosis. (shaath2024integratinggenomesequencing pages 2-4, shaath2024integratinggenomesequencing pages 5-7)

12. Treatment

12.1 Pharmacotherapy (symptomatic)

No disease-modifying pharmacotherapy specific to ADGRG1-BFPP was identified in the retrieved evidence. Current treatment is symptomatic, primarily targeting seizures.

Antiseizure medications (ASMs): - Valproate was “initially responsive” in one ADGRG1 case report; other reported ASMs used across severe cases include vigabatrin, levetiracetam, topiramate, clonazepam, and perampanel, with many patients remaining refractory. (carneiro2021casereportdiffuse pages 2-3, carneiro2021casereportdiffuse pages 1-2) - A separate ADGRG1 regulatory-variant–associated polymicrogyria phenotype (perisylvian-restricted) is reported to have vigabatrin efficacy in GPR56-mutated patients (reported in model-focused review context). (murayama2020thepolymicrogyriaassociatedgpr56 pages 1-2)

Suggested MAXO terms (treatment): - MAXO: antiseizure medication therapy (carneiro2021casereportdiffuse pages 1-2) - MAXO: supportive care / multidisciplinary rehabilitation (inferred standard of care; disease-specific trials absent) (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 1-3)

12.2 Surgical/interventional

No ADGRG1-specific epilepsy surgery outcomes were identified in the retrieved evidence excerpts.

12.3 Experimental therapeutics

No interventional clinical trials targeting ADGRG1-BFPP were identified. An observational study in congenital/early-onset ataxias included sequencing GPR56 in participants with suggestive features (NCT01488461; first posted 2011-12-08, completion 2014-10). (NCT01488461 chunk 1)

13. Prevention

Primary prevention of the genetic disorder is not possible without reproductive interventions; prevention focuses on recurrence reduction through genetic counseling and family testing. - Genetic counseling and carrier/cascade testing are recommended and emphasized, especially in consanguineous families. (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 1-3, khatib2024adgrg1relatedpolymicrogyriasyndrome pages 6-7) - Prenatal testing / reproductive planning is enabled once a familial pathogenic ADGRG1 variant is established; family reports highlight reproductive utility of molecular diagnosis. (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 4-6, khatib2024adgrg1relatedpolymicrogyriasyndrome pages 6-7)

Suggested MAXO terms (prevention): - MAXO: genetic counseling; MAXO: carrier screening; MAXO: prenatal genetic testing (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 6-7, khatib2024adgrg1relatedpolymicrogyriasyndrome pages 1-3)

14. Other species / natural disease

No naturally occurring veterinary disease analogs explicitly tied to ADGRG1 variants were identified in the retrieved evidence.

15. Model organisms

15.1 Model systems and key phenotypes

• Mouse (Gpr56 loss): reported to cause reduced progenitor proliferation, radial glial endfeet/pial basement membrane abnormalities, neuron overmigration, disorganized lamination, and a “cobblestone-like malformation.” (murayama2020thepolymicrogyriaassociatedgpr56 pages 1-2)
• Zebrafish/rodent glial models: ADGRG1/GPR56 is implicated as a conserved regulator of myelination and glial development; in PNS Schwann cells, GPR56-dependent RhoA signaling supports radial sorting and myelin thickness/organization, and mutants show progressive neuropathy-like phenotypes. (ackerman2018gpr56adgrg1regulatesdevelopment pages 1-2, ackerman2018gpr56adgrg1regulatesdevelopment pages 10-11)
• Microglia–OPC axis (mouse): microglia-derived TG2 signals to ADGRG1 on OPCs (with laminin) promoting OPC proliferation and improving remyelination in murine demyelination models. (giera2018microglialtransglutaminase2drives pages 1-2, giera2018microglialtransglutaminase2drives pages 3-5)
• Common marmoset (transgenic promoter model): a polymicrogyria-associated GPR56 promoter element preferentially drives expression in developing GABAergic neurons, supporting interneuron involvement in epilepsy linked to GPR56 regulatory variants. (murayama2020thepolymicrogyriaassociatedgpr56 pages 1-2)

15.2 Model applications and limitations

These models support mechanistic interrogation of (i) cortical lamination and migration, (ii) ECM ligand interactions and Gα12/13–RhoA signaling, and (iii) myelination/glia–glia signaling (microglia→OPC; Schwann cells). However, no model fully recapitulates the complete human BFPP MRI signature (frontoparietal gradient plus hindbrain hypoplasia) in the retrieved excerpts, and species differences in ligand interactions (e.g., TG2 binding specificity in some systems) have been reported in mechanistic studies. (chiang2011diseaseassociatedgpr56mutations pages 7-8, ackerman2018gpr56adgrg1regulatesdevelopment pages 1-2)

Recent developments (2023–2024 prioritized highlights)

• 2024 (family + review): identification of a novel homozygous ADGRG1 variant (p.Leu103Pro) in a large consanguineous family; detailed modern WES pipeline and emphasis on genetic counseling and diagnostic pitfalls (MRI mimicry of infections; occasional normal infancy MRI). (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 1-3, khatib2024adgrg1relatedpolymicrogyriasyndrome pages 4-6)
• 2024 (multi-omics rare disease): integrated WGS + untargeted metabolomics in twins with homozygous ADGRG1 p.Arg565Trp and complex overlapping phenotype; metabolomics flagged 180 clinically relevant biochemicals with substantial lipid (48%) and amino-acid pathway (29%) perturbations, and evidence for oxidative stress/glutathione depletion markers and urea-cycle/arginine–proline metabolism involvement. (shaath2024integratinggenomesequencing pages 5-7, shaath2024integratinggenomesequencing pages 7-8, shaath2024integratinggenomesequencing pages 4-5)
• 2024 (signaling pharmacology): GPR56 ligand modalities show biased G-protein selectivity (G13 vs G12) while converging on Rho pathway activation, providing tools and conceptual frameworks potentially relevant to future targeted modulation strategies (not yet applied clinically to BFPP). (jallouli2024gproteinselectivity pages 1-2, jallouli2024gproteinselectivity pages 11-13)
• 2023 (cohort genetics): large polymicrogyria cohort study demonstrated 32.7% genetic diagnostic yield and highlighted convergent mechanistic categories including ion-conducting proteins; ADGRG1 remains a canonical known PMG gene within such cohorts. (akula2023exomesequencingand pages 2-3)

Expert synthesis / interpretation (authoritative-source-driven)

Taken together, the human genetics literature establishes ADGRG1 as a high-confidence Mendelian cause of BFPP with a recognizable radiogenomic signature and high burden of epilepsy and developmental disability (piao2005genotype–phenotypeanalysisof pages 3-5, piao2005genotype–phenotypeanalysisof pages 1-2). Functional biochemical studies support that many disease alleles are “processing/trafficking” loss-of-function variants in an adhesion GPCR requiring precise proteolytic maturation and extracellular interactions; this molecular fragility plausibly explains why both extracellular missense and truncating variants can converge on a similar neurodevelopmental outcome (chiang2011diseaseassociatedgpr56mutations pages 3-5, ke2008biochemicalcharacterizationof pages 1-2, chiang2011diseaseassociatedgpr56mutations pages 1-2). Recent signaling studies (2024) deepen mechanistic resolution of how distinct ADGRG1 activation modalities (antibody vs small molecule vs constitutive) can yield biased G-protein engagement while preserving Rho-pathway output, suggesting that future therapeutic exploration would likely need to consider ligand modality, receptor cleavage state, and cell-type-specific signaling context (jallouli2024gproteinselectivity pages 1-2, jallouli2024gproteinselectivity pages 7-9). At present, however, clinical management remains supportive and seizure-focused, and prevention is primarily via genetic counseling and reproductive planning in affected families. (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 6-7, carneiro2021casereportdiffuse pages 1-2)

References

1. (piao2005genotype–phenotypeanalysisof pages 3-5): Xianhua Piao, Bernard S. Chang, Adria Bodell, Katelyn Woods, Bruria BenZeev, Meral Topcu, Renzo Guerrini, Hadassa Goldberg‐Stern, Laszlo Sztriha, William B. Dobyns, A. James Barkovich, and Christopher A. Walsh. Genotype–phenotype analysis of human frontoparietal polymicrogyria syndromes. Annals of Neurology, 58:680-687, Nov 2005. URL: https://doi.org/10.1002/ana.20616, doi:10.1002/ana.20616. This article has 174 citations and is from a highest quality peer-reviewed journal.

2. (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 1-3): Dalida El Khatib, Moussa Hojeij, Sandra Sabbagh, Cybel Mehawej, Eliane Chouery, Seung Woo Ryu, JiHye Kim, and Andre Mégarbané. Adgrg1-related polymicrogyria syndrome: report on a large consanguineous family with a novel variant and review. Egyptian Journal of Medical Human Genetics, Apr 2024. URL: https://doi.org/10.1186/s43042-024-00499-1, doi:10.1186/s43042-024-00499-1. This article has 1 citations and is from a peer-reviewed journal.

3. (piao2005genotype–phenotypeanalysisof pages 1-2): Xianhua Piao, Bernard S. Chang, Adria Bodell, Katelyn Woods, Bruria BenZeev, Meral Topcu, Renzo Guerrini, Hadassa Goldberg‐Stern, Laszlo Sztriha, William B. Dobyns, A. James Barkovich, and Christopher A. Walsh. Genotype–phenotype analysis of human frontoparietal polymicrogyria syndromes. Annals of Neurology, 58:680-687, Nov 2005. URL: https://doi.org/10.1002/ana.20616, doi:10.1002/ana.20616. This article has 174 citations and is from a highest quality peer-reviewed journal.

4. (OpenTargets Search: polymicrogyria,bilateral frontoparietal polymicrogyria-ADGRG1): Open Targets Query (polymicrogyria,bilateral frontoparietal polymicrogyria-ADGRG1, 2 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

5. (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 6-7): Dalida El Khatib, Moussa Hojeij, Sandra Sabbagh, Cybel Mehawej, Eliane Chouery, Seung Woo Ryu, JiHye Kim, and Andre Mégarbané. Adgrg1-related polymicrogyria syndrome: report on a large consanguineous family with a novel variant and review. Egyptian Journal of Medical Human Genetics, Apr 2024. URL: https://doi.org/10.1186/s43042-024-00499-1, doi:10.1186/s43042-024-00499-1. This article has 1 citations and is from a peer-reviewed journal.

6. (jansen2005geneticsofthe pages 5-6): An C. Jansen and E. Andermann. Genetics of the polymicrogyria syndromes. Journal of Medical Genetics, 42:369-378, May 2005. URL: https://doi.org/10.1136/jmg.2004.023952, doi:10.1136/jmg.2004.023952. This article has 205 citations and is from a domain leading peer-reviewed journal.

7. (carneiro2021casereportdiffuse pages 1-2): Fábio Carneiro, Júlia Duarte, Francisco Laranjeira, Sofia Barbosa-Gouveia, María-Luz Couce, and Maria José Fonseca. Case report: diffuse polymicrogyria associated with a novel adgrg1 variant. Frontiers in Pediatrics, Aug 2021. URL: https://doi.org/10.3389/fped.2021.728077, doi:10.3389/fped.2021.728077. This article has 7 citations.

8. (chiang2011diseaseassociatedgpr56mutations pages 1-2): Nien-Yi Chiang, Cheng-Chih Hsiao, Yi-Shu Huang, Hsin-Yi Chen, I-Ju Hsieh, Gin-Wen Chang, and Hsi-Hsien Lin. Disease-associated gpr56 mutations cause bilateral frontoparietal polymicrogyria via multiple mechanisms. Journal of Biological Chemistry, 286:14215-14225, Apr 2011. URL: https://doi.org/10.1074/jbc.m110.183830, doi:10.1074/jbc.m110.183830. This article has 103 citations and is from a domain leading peer-reviewed journal.

9. (carneiro2021casereportdiffuse pages 2-3): Fábio Carneiro, Júlia Duarte, Francisco Laranjeira, Sofia Barbosa-Gouveia, María-Luz Couce, and Maria José Fonseca. Case report: diffuse polymicrogyria associated with a novel adgrg1 variant. Frontiers in Pediatrics, Aug 2021. URL: https://doi.org/10.3389/fped.2021.728077, doi:10.3389/fped.2021.728077. This article has 7 citations.

10. (carneiro2021casereportdiffuse pages 3-5): Fábio Carneiro, Júlia Duarte, Francisco Laranjeira, Sofia Barbosa-Gouveia, María-Luz Couce, and Maria José Fonseca. Case report: diffuse polymicrogyria associated with a novel adgrg1 variant. Frontiers in Pediatrics, Aug 2021. URL: https://doi.org/10.3389/fped.2021.728077, doi:10.3389/fped.2021.728077. This article has 7 citations.

11. (carneiro2021casereportdiffuse pages 5-6): Fábio Carneiro, Júlia Duarte, Francisco Laranjeira, Sofia Barbosa-Gouveia, María-Luz Couce, and Maria José Fonseca. Case report: diffuse polymicrogyria associated with a novel adgrg1 variant. Frontiers in Pediatrics, Aug 2021. URL: https://doi.org/10.3389/fped.2021.728077, doi:10.3389/fped.2021.728077. This article has 7 citations.

12. (parrini2009bilateralfrontoparietalpolymicrogyria pages 6-8): Elena Parrini, Anna Rita Ferrari, Thomas Dorn, Christopher A. Walsh, and Renzo Guerrini. Bilateral frontoparietal polymicrogyria, lennox‐gastaut syndrome, and gpr56 gene mutations. Epilepsia, 50:1344-1353, Jun 2009. URL: https://doi.org/10.1111/j.1528-1167.2008.01787.x, doi:10.1111/j.1528-1167.2008.01787.x. This article has 75 citations and is from a domain leading peer-reviewed journal.

13. (parrini2009bilateralfrontoparietalpolymicrogyria pages 3-5): Elena Parrini, Anna Rita Ferrari, Thomas Dorn, Christopher A. Walsh, and Renzo Guerrini. Bilateral frontoparietal polymicrogyria, lennox‐gastaut syndrome, and gpr56 gene mutations. Epilepsia, 50:1344-1353, Jun 2009. URL: https://doi.org/10.1111/j.1528-1167.2008.01787.x, doi:10.1111/j.1528-1167.2008.01787.x. This article has 75 citations and is from a domain leading peer-reviewed journal.

14. (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 3-4): Dalida El Khatib, Moussa Hojeij, Sandra Sabbagh, Cybel Mehawej, Eliane Chouery, Seung Woo Ryu, JiHye Kim, and Andre Mégarbané. Adgrg1-related polymicrogyria syndrome: report on a large consanguineous family with a novel variant and review. Egyptian Journal of Medical Human Genetics, Apr 2024. URL: https://doi.org/10.1186/s43042-024-00499-1, doi:10.1186/s43042-024-00499-1. This article has 1 citations and is from a peer-reviewed journal.

15. (khatib2024adgrg1relatedpolymicrogyriasyndrome pages 4-6): Dalida El Khatib, Moussa Hojeij, Sandra Sabbagh, Cybel Mehawej, Eliane Chouery, Seung Woo Ryu, JiHye Kim, and Andre Mégarbané. Adgrg1-related polymicrogyria syndrome: report on a large consanguineous family with a novel variant and review. Egyptian Journal of Medical Human Genetics, Apr 2024. URL: https://doi.org/10.1186/s43042-024-00499-1, doi:10.1186/s43042-024-00499-1. This article has 1 citations and is from a peer-reviewed journal.

16. (piao2005genotype–phenotypeanalysisof media 547d7d36): Xianhua Piao, Bernard S. Chang, Adria Bodell, Katelyn Woods, Bruria BenZeev, Meral Topcu, Renzo Guerrini, Hadassa Goldberg‐Stern, Laszlo Sztriha, William B. Dobyns, A. James Barkovich, and Christopher A. Walsh. Genotype–phenotype analysis of human frontoparietal polymicrogyria syndromes. Annals of Neurology, 58:680-687, Nov 2005. URL: https://doi.org/10.1002/ana.20616, doi:10.1002/ana.20616. This article has 174 citations and is from a highest quality peer-reviewed journal.

17. (lin2021atwinscase pages 7-10): Wenxin Lin, Yingying Chai, Xia Zhang, Tingting Huang, Guo Zheng, Gang Zhang, Fang Peng, and Yanjun Huang. A twins case of lissencephaly with gpr56 compound heterozygous mutations and literatures review. ArXiv, Jan 2021. URL: https://doi.org/10.21203/rs.3.rs-144069/v1, doi:10.21203/rs.3.rs-144069/v1. This article has 0 citations.

18. (chiang2011diseaseassociatedgpr56mutations pages 8-10): Nien-Yi Chiang, Cheng-Chih Hsiao, Yi-Shu Huang, Hsin-Yi Chen, I-Ju Hsieh, Gin-Wen Chang, and Hsi-Hsien Lin. Disease-associated gpr56 mutations cause bilateral frontoparietal polymicrogyria via multiple mechanisms. Journal of Biological Chemistry, 286:14215-14225, Apr 2011. URL: https://doi.org/10.1074/jbc.m110.183830, doi:10.1074/jbc.m110.183830. This article has 103 citations and is from a domain leading peer-reviewed journal.

19. (chiang2011diseaseassociatedgpr56mutations pages 3-5): Nien-Yi Chiang, Cheng-Chih Hsiao, Yi-Shu Huang, Hsin-Yi Chen, I-Ju Hsieh, Gin-Wen Chang, and Hsi-Hsien Lin. Disease-associated gpr56 mutations cause bilateral frontoparietal polymicrogyria via multiple mechanisms. Journal of Biological Chemistry, 286:14215-14225, Apr 2011. URL: https://doi.org/10.1074/jbc.m110.183830, doi:10.1074/jbc.m110.183830. This article has 103 citations and is from a domain leading peer-reviewed journal.

20. (chiang2011diseaseassociatedgpr56mutations pages 10-11): Nien-Yi Chiang, Cheng-Chih Hsiao, Yi-Shu Huang, Hsin-Yi Chen, I-Ju Hsieh, Gin-Wen Chang, and Hsi-Hsien Lin. Disease-associated gpr56 mutations cause bilateral frontoparietal polymicrogyria via multiple mechanisms. Journal of Biological Chemistry, 286:14215-14225, Apr 2011. URL: https://doi.org/10.1074/jbc.m110.183830, doi:10.1074/jbc.m110.183830. This article has 103 citations and is from a domain leading peer-reviewed journal.

21. (ke2008biochemicalcharacterizationof pages 1-2): Ning Ke, Hongwen Ma, Gundo Diedrich, John Chionis, Guohong Liu, De-Hua Yu, Flossie Wong-Staal, and Qi-Xiang Li. Biochemical characterization of genetic mutations of gpr56 in patients with bilateral frontoparietal polymicrogyria (bfpp). Biochemical and biophysical research communications, 366 2:314-20, Feb 2008. URL: https://doi.org/10.1016/j.bbrc.2007.11.071, doi:10.1016/j.bbrc.2007.11.071. This article has 35 citations and is from a peer-reviewed journal.

22. (shaath2024integratinggenomesequencing pages 2-4): Rulan Shaath, Aljazi Al-Maraghi, Haytham Ali, Jehan AlRayahi, Adam D. Kennedy, Karen L. DeBalsi, Sura Hussein, Najwa Elbashir, Sujitha S. Padmajeya, Sasirekha Palaniswamy, Sarah H. Elsea, Ammira A. Akil, Noha A. Yousri, and Khalid A. Fakhro. Integrating genome sequencing and untargeted metabolomics in monozygotic twins with a rare complex neurological disorder. Metabolites, 14:152, Mar 2024. URL: https://doi.org/10.3390/metabo14030152, doi:10.3390/metabo14030152. This article has 5 citations.

23. (shaath2024integratinggenomesequencing pages 4-5): Rulan Shaath, Aljazi Al-Maraghi, Haytham Ali, Jehan AlRayahi, Adam D. Kennedy, Karen L. DeBalsi, Sura Hussein, Najwa Elbashir, Sujitha S. Padmajeya, Sasirekha Palaniswamy, Sarah H. Elsea, Ammira A. Akil, Noha A. Yousri, and Khalid A. Fakhro. Integrating genome sequencing and untargeted metabolomics in monozygotic twins with a rare complex neurological disorder. Metabolites, 14:152, Mar 2024. URL: https://doi.org/10.3390/metabo14030152, doi:10.3390/metabo14030152. This article has 5 citations.

24. (murayama2020thepolymicrogyriaassociatedgpr56 pages 1-2): Ayako Y. Murayama, Ken-ichiro Kuwako, Junko Okahara, Byoung-Il Bae, Misako Okuno, Hiromi Mashiko, Tomomi Shimogori, Christopher A. Walsh, Erika Sasaki, and Hideyuki Okano. The polymicrogyria-associated gpr56 promoter preferentially drives gene expression in developing gabaergic neurons in common marmosets. Scientific Reports, Dec 2020. URL: https://doi.org/10.1038/s41598-020-78608-4, doi:10.1038/s41598-020-78608-4. This article has 17 citations and is from a peer-reviewed journal.

25. (chiang2011diseaseassociatedgpr56mutations pages 5-6): Nien-Yi Chiang, Cheng-Chih Hsiao, Yi-Shu Huang, Hsin-Yi Chen, I-Ju Hsieh, Gin-Wen Chang, and Hsi-Hsien Lin. Disease-associated gpr56 mutations cause bilateral frontoparietal polymicrogyria via multiple mechanisms. Journal of Biological Chemistry, 286:14215-14225, Apr 2011. URL: https://doi.org/10.1074/jbc.m110.183830, doi:10.1074/jbc.m110.183830. This article has 103 citations and is from a domain leading peer-reviewed journal.

26. (chiang2011diseaseassociatedgpr56mutations pages 7-8): Nien-Yi Chiang, Cheng-Chih Hsiao, Yi-Shu Huang, Hsin-Yi Chen, I-Ju Hsieh, Gin-Wen Chang, and Hsi-Hsien Lin. Disease-associated gpr56 mutations cause bilateral frontoparietal polymicrogyria via multiple mechanisms. Journal of Biological Chemistry, 286:14215-14225, Apr 2011. URL: https://doi.org/10.1074/jbc.m110.183830, doi:10.1074/jbc.m110.183830. This article has 103 citations and is from a domain leading peer-reviewed journal.

27. (jallouli2024gproteinselectivity pages 1-2): Raida Jallouli, Ana L. Moreno-Salinas, Andréanne Laniel, Brian Holleran, Charlotte Avet, Joan Jacob, Trang Hoang, Christine Lavoie, Kendra S. Carmon, Michel Bouvier, and Richard Leduc. G protein selectivity profile of gpr56/adgrg1 and its effect on downstream effectors. Cellular and Molecular Life Sciences: CMLS, Sep 2024. URL: https://doi.org/10.1007/s00018-024-05416-8, doi:10.1007/s00018-024-05416-8. This article has 10 citations.

28. (einspahr2022pathophysiologicalimpactof pages 5-9): Jeanette M. Einspahr and Douglas G. Tilley. Pathophysiological impact of the adhesion g protein-coupled receptor family. Aug 2022. URL: https://doi.org/10.1152/ajpcell.00445.2021, doi:10.1152/ajpcell.00445.2021. This article has 31 citations.

29. (giera2018microglialtransglutaminase2drives pages 1-2): Stefanie Giera, Rong Luo, Yanqin Ying, Sarah D Ackerman, Sung-Jin Jeong, Hannah M Stoveken, Christopher J Folts, Christina A Welsh, Gregory G Tall, Beth Stevens, Kelly R Monk, and Xianhua Piao. Microglial transglutaminase-2 drives myelination and myelin repair via gpr56/adgrg1 in oligodendrocyte precursor cells. eLife, May 2018. URL: https://doi.org/10.7554/elife.33385, doi:10.7554/elife.33385. This article has 164 citations and is from a domain leading peer-reviewed journal.

30. (giera2018microglialtransglutaminase2drives pages 3-5): Stefanie Giera, Rong Luo, Yanqin Ying, Sarah D Ackerman, Sung-Jin Jeong, Hannah M Stoveken, Christopher J Folts, Christina A Welsh, Gregory G Tall, Beth Stevens, Kelly R Monk, and Xianhua Piao. Microglial transglutaminase-2 drives myelination and myelin repair via gpr56/adgrg1 in oligodendrocyte precursor cells. eLife, May 2018. URL: https://doi.org/10.7554/elife.33385, doi:10.7554/elife.33385. This article has 164 citations and is from a domain leading peer-reviewed journal.

31. (bauer2024mesenchymaltransglutaminase2 pages 1-2): Lea Bauer, Jessica Edwards, Andreas Heil, Sharon Dewitt, Heike Biebermann, Daniel Aeschlimann, and Vera Knäuper. Mesenchymal transglutaminase 2 activates epithelial adam17: link to g-protein-coupled receptor 56 (adgrg1) signalling. International Journal of Molecular Sciences, 25:2329, Feb 2024. URL: https://doi.org/10.3390/ijms25042329, doi:10.3390/ijms25042329. This article has 5 citations.

32. (bauer2024mesenchymaltransglutaminase2 pages 2-5): Lea Bauer, Jessica Edwards, Andreas Heil, Sharon Dewitt, Heike Biebermann, Daniel Aeschlimann, and Vera Knäuper. Mesenchymal transglutaminase 2 activates epithelial adam17: link to g-protein-coupled receptor 56 (adgrg1) signalling. International Journal of Molecular Sciences, 25:2329, Feb 2024. URL: https://doi.org/10.3390/ijms25042329, doi:10.3390/ijms25042329. This article has 5 citations.

33. (bauer2024mesenchymaltransglutaminase2 pages 6-9): Lea Bauer, Jessica Edwards, Andreas Heil, Sharon Dewitt, Heike Biebermann, Daniel Aeschlimann, and Vera Knäuper. Mesenchymal transglutaminase 2 activates epithelial adam17: link to g-protein-coupled receptor 56 (adgrg1) signalling. International Journal of Molecular Sciences, 25:2329, Feb 2024. URL: https://doi.org/10.3390/ijms25042329, doi:10.3390/ijms25042329. This article has 5 citations.

34. (ackerman2018gpr56adgrg1regulatesdevelopment pages 1-2): Sarah D. Ackerman, Rong Luo, Yannick Poitelon, Amit Mogha, Breanne L. Harty, Mitchell D’Rozario, Nicholas E. Sanchez, Asvin K.K. Lakkaraju, Paul Gamble, Jun Li, Jun Qu, Matthew R. MacEwan, Wilson Zachary Ray, Adriano Aguzzi, M. Laura Feltri, Xianhua Piao, and Kelly R. Monk. Gpr56/adgrg1 regulates development and maintenance of peripheral myelin. The Journal of Experimental Medicine, 215:941-961, Mar 2018. URL: https://doi.org/10.1084/jem.20161714, doi:10.1084/jem.20161714. This article has 73 citations.

35. (akula2023exomesequencingand pages 2-3): Shyam K. Akula, Allen Y. Chen, Jennifer E. Neil, Diane D. Shao, Alisa Mo, Norma K. Hylton, Stephanie DiTroia, Vijay S. Ganesh, Richard S. Smith, Katherine O’Kane, Rebecca C. Yeh, Jack H. Marciano, Samantha Kirkham, Connor J. Kenny, Janet H. T. Song, Muna Al Saffar, Francisca Millan, David J. Harris, Andrea V. Murphy, Kara C. Klemp, Stephen R. Braddock, Harrison Brand, Isaac Wong, Michael E. Talkowski, Anne O’Donnell-Luria, Abbe Lai, Robert Sean Hill, Ganeshwaran H. Mochida, Ryan N. Doan, A. James Barkovich, Edward Yang, Dina Amrom, Eva Andermann, Annapurna Poduri, Christopher A. Walsh, Bassam Abu-Libdeh, Lihadh Al-Gazali, Muna Al Saffar, Edith Alva Moncayo, Dina Amrom, Eva Anderman, Anna-Kaisa Anttonen, Saunder Barnes, Sara Barnett, Todd Barron, Brenda J. Barry, Lina Basel-Vanagaite, Laila Bastaki, Luis Bello-Espinosa, Tawfeg Ben-Omran, Matthew Bernard, Carsten G. Bonneman, Blaise Bourgeois, Stephen Brown, Roberto H. Caraballo, Gergory Cascino, Michael Clarke, Monika Cohen, Yanick Crow, Bernard Dan, Kira A. Dies, William B. Dobyns, François Dubeau, Christelle El Achkar, Gregory M. Enns, Laurence Faivre, Laura Flores-Sarnat, John Gaitanis, Kuchukhidze Giorgi, Andrew Green, Alan Guberman, Renzo Guerrini, Micheil Innes, Richard Jacobsen, Sebastian Jacquemont, Samir Khalil, Joerg Klepper, Dimitri Kranic, Kalpathy Krishnamoorthy, Anna-Elina Lehesjoki, Dorit Lev, Richard J. Leventer, Emily Lisi, Valerie Loik Ramey, Sally Ann Lynch, Laila Mahmoud, David Manchester, David Mandelbaum, Daphna Marom, Deborah Marsden, Mayra Martinez Ojeda, Amira Masri, Livija Medne, Denis Melanson, David T. Miller, Anna Minster, Edward Neilan, Dang Khoa Nguyen, Heather E. Olson, Ignacio Pascual-Castroviejo, Philip L. Pearl, Daniela Pilz, Nada Quercia, Salmo Raskin, Miriam Regev, Lance Rodan, Cynthia Rooney, Michael Rutlin, Mustafa Sahin, Mustafa A. Salih, Pierre Sarda, Harvey B. Sarnat, Ingrid Scheffer, Joseph Shieh, Sharon E. Smith, Janet S. Soul, Siddharth Srivastava, Laszlo Sztriha, Donatella Tampieri, John Tolmie, Meral Topçu, Eugen Trinka, John Tsai, Jack Tsao, Sheila Unger, Iris Unterberger, Goekhan Uyanik, Kette Valente, Thomas Voit, Louise Wilson, and Grace Yoon. Exome sequencing and the identification of new genes and shared mechanisms in polymicrogyria. JAMA Neurology, 80:980, Sep 2023. URL: https://doi.org/10.1001/jamaneurol.2023.2363, doi:10.1001/jamaneurol.2023.2363. This article has 39 citations and is from a highest quality peer-reviewed journal.

36. (NCT01488461 chunk 1): Phenotypic and Genotypic Studies in Congenital and Early Onset Ataxias. Assistance Publique - Hôpitaux de Paris. 2012. ClinicalTrials.gov Identifier: NCT01488461

37. (shaath2024integratinggenomesequencing pages 5-7): Rulan Shaath, Aljazi Al-Maraghi, Haytham Ali, Jehan AlRayahi, Adam D. Kennedy, Karen L. DeBalsi, Sura Hussein, Najwa Elbashir, Sujitha S. Padmajeya, Sasirekha Palaniswamy, Sarah H. Elsea, Ammira A. Akil, Noha A. Yousri, and Khalid A. Fakhro. Integrating genome sequencing and untargeted metabolomics in monozygotic twins with a rare complex neurological disorder. Metabolites, 14:152, Mar 2024. URL: https://doi.org/10.3390/metabo14030152, doi:10.3390/metabo14030152. This article has 5 citations.

38. (ackerman2018gpr56adgrg1regulatesdevelopment pages 10-11): Sarah D. Ackerman, Rong Luo, Yannick Poitelon, Amit Mogha, Breanne L. Harty, Mitchell D’Rozario, Nicholas E. Sanchez, Asvin K.K. Lakkaraju, Paul Gamble, Jun Li, Jun Qu, Matthew R. MacEwan, Wilson Zachary Ray, Adriano Aguzzi, M. Laura Feltri, Xianhua Piao, and Kelly R. Monk. Gpr56/adgrg1 regulates development and maintenance of peripheral myelin. The Journal of Experimental Medicine, 215:941-961, Mar 2018. URL: https://doi.org/10.1084/jem.20161714, doi:10.1084/jem.20161714. This article has 73 citations.

39. (shaath2024integratinggenomesequencing pages 7-8): Rulan Shaath, Aljazi Al-Maraghi, Haytham Ali, Jehan AlRayahi, Adam D. Kennedy, Karen L. DeBalsi, Sura Hussein, Najwa Elbashir, Sujitha S. Padmajeya, Sasirekha Palaniswamy, Sarah H. Elsea, Ammira A. Akil, Noha A. Yousri, and Khalid A. Fakhro. Integrating genome sequencing and untargeted metabolomics in monozygotic twins with a rare complex neurological disorder. Metabolites, 14:152, Mar 2024. URL: https://doi.org/10.3390/metabo14030152, doi:10.3390/metabo14030152. This article has 5 citations.

40. (jallouli2024gproteinselectivity pages 11-13): Raida Jallouli, Ana L. Moreno-Salinas, Andréanne Laniel, Brian Holleran, Charlotte Avet, Joan Jacob, Trang Hoang, Christine Lavoie, Kendra S. Carmon, Michel Bouvier, and Richard Leduc. G protein selectivity profile of gpr56/adgrg1 and its effect on downstream effectors. Cellular and Molecular Life Sciences: CMLS, Sep 2024. URL: https://doi.org/10.1007/s00018-024-05416-8, doi:10.1007/s00018-024-05416-8. This article has 10 citations.

41. (jallouli2024gproteinselectivity pages 7-9): Raida Jallouli, Ana L. Moreno-Salinas, Andréanne Laniel, Brian Holleran, Charlotte Avet, Joan Jacob, Trang Hoang, Christine Lavoie, Kendra S. Carmon, Michel Bouvier, and Richard Leduc. G protein selectivity profile of gpr56/adgrg1 and its effect on downstream effectors. Cellular and Molecular Life Sciences: CMLS, Sep 2024. URL: https://doi.org/10.1007/s00018-024-05416-8, doi:10.1007/s00018-024-05416-8. This article has 10 citations.

Artifacts

• Edison artifact artifact-00
• Edison artifact artifact-01
• Edison artifact artifact-02
• Edison artifact artifact-03