ArticleAnnals of neurology2019
Variation in SIPA1L2 is correlated with phenotype modification in Charcot- Marie- Tooth disease type 1A.
Article in Annals of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Unraveling the Genetic Landscape of Foot Arch Morphology: A Systematic Review of Single Nucleotide Polymorphisms.Clinical genetics · 2025Pooled it
- Charcot-Marie-Tooth disease and related neuropathies.Nature reviews. Disease primers · 2026Review
- Search for Additional Pathogenic Variants to Explain Variation inNeurology. Genetics · 2025Article
- Striae gravidarum in the Han Chinese pregnant population: identifying genetic markers and risk factors through a prospective cohort study.BMC pregnancy and childbirth · 2025Article
- NetREm: Network Regression Embeddings reveal cell-type transcription factor coordination for gene regulation.Bioinformatics advances · 2025Article
- KCNJ2 Facilitates Clear Cell Renal Cell Carcinoma Progression and Glucose Metabolism.International journal of genomics · 2025Article
- Effects of SIPA1L1 on trabecular meshwork extracellular matrix protein accumulation and cellular phagocytosis in POAG.JCI insight · 2024Article
- A study concept of expeditious clinical enrollment for genetic modifier studies in Charcot-Marie-Tooth neuropathy 1A.Journal of the peripheral nervous system : JPNS · 2024Article
- Peripheral Nervous System (PNS) Myelin Diseases.Cold Spring Harbor perspectives in biology · 2024Review
- Intermediate conduction velocity in two cases of Charcot-Marie-Tooth disease type 1A.European journal of neurology · 2024Article
- Testing SIPA1L2 as a modifier of CMT1A using mouse models.Journal of neuropathology and experimental neurology · 2024Article
- Article
- Irisin enhances chondrogenic differentiation of human mesenchymal stem cells via Rap1/PI3K/AKT axis.Stem cell research & therapy · 2022Article
- A nonsense mutation in MME gene associates with autosomal recessive late-onset Charcot-Marie-Tooth disease.Molecular genetics & genomic medicine · 2022Article
- Mechanisms and Treatments in Demyelinating CMT.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Genome-Edited Coincidence and PMP22-HiBiT Fusion Reporter Cell Lines Enable an Artifact-Suppressive Quantitative High-Throughput Screening Strategy forACS pharmacology & translational science · 2021Article
- A novel case of concurrent occurrence of demyelinating-polyneuropathy-causing PMP22 duplication and SOX10 gene mutation producing severe hypertrophic neuropathy.BMC neurology · 2021Article
- The Pathological Features of Common Hereditary Mitochondrial Dynamics Neuropathy.Frontiers in neuroscience · 2021Article
- Genetic modifiers and phenotypic variability in neuromuscular disorders.Journal of applied genetics · 2020Review
- Paternal gender specificity and mild phenotypes in Charcot-Marie-Tooth type 1A patients with de novo 17p12 rearrangements.Molecular genetics & genomic medicine · 2020Article
Corrections and comments
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Authors and funding
30 authors at 18 institutions in 5 countries.
Funding
Abstract
objectiveGenetic modifiers in rare disease have long been suspected to contribute to the considerable variance in disease expression, including Charcot-Marie-Tooth disease type 1A (CMT1A). To address this question, the Inherited Neuropathy Consortium collected a large standardized sample of such rare CMT1A patients over a period of 8 years. CMT1A is caused in most patients by a uniformly sized 1.5 Mb duplication event involving the gene PMP22.
methodsWe genotyped DNA samples from 971 CMT1A patients on Illumina BeadChips. Genome-wide analysis was performed in a subset of 330 of these patients, who expressed the extremes of a hallmark symptom: mild and severe foot dorsiflexion strength impairment. SIPA1L2 (signal-induced proliferation-associated 1 like 2), the top identified candidate modifier gene, was expressed in the peripheral nerve, and our functional studies identified and confirmed interacting proteins using coimmunoprecipitation analysis, mass spectrometry, and immunocytochemistry. Chromatin immunoprecipitation and in vitro siRNA experiments were used to analyze gene regulation.
resultsWe identified significant association of 4 single nucleotide polymorphisms (rs10910527, rs7536385, rs4649265, rs1547740) in SIPA1L2 with foot dorsiflexion strength (p < 1 × 10
interpretationSIPA1L2 is a potential genetic modifier of CMT1A phenotypic expressions and offers a new pathway to therapeutic interventions. ANN NEUROL 2019;85:316-330.
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