Question explored with the scientific record
is there a connection of fibrillin 1 mutations and sciatica
The short version: no study in this evidence block tests whether FBN1 mutations cause sciatica. The connection is mechanically plausible but unproven by the papers you received.
None of the 29 records touch sciatica (nerve root compression from the lumbar spine causing leg pain). They describe Marfan syndrome mutations in the fibrillin-1 gene—over 50 different variants including cysteine substitutions, frameshifts, and splice-site defects [1, 4, 11, 15, 19, 21]—but every paper focuses on aortic dilation, lens dislocation, skeletal features, or gene-expression changes in cultured skin fibroblasts [20]. Not one examines the spine or the L4-S1 nerve roots.
The plausible link is that Marfan patients have lax ligaments, dural ectasia (stretching of the spinal sac), and abnormal spinal loading, all of which could compress a nerve root and produce sciatica. Study [10] does mention dural ectasia grade 2 in several patients with frameshift mutations, but it never asks whether those patients had radicular leg pain. That is the gap: the data that would test the hypothesis was never collected or never published.
The 2006 review [12] notes that FBN1 mutations disrupt microfibril assembly and dysregulate TGF-beta signaling, a pathway that contributes to ligament laxity and bone remodeling. Outside this retrieval, connective-tissue disorders are associated with higher rates of back pain and radiculopathy, but the evidence here says nothing specific about sciatica as an outcome.
Without studies that actually compare sciatica rates in FBN1-mutation carriers versus matched controls, the claim remains a reasonable hypothesis with zero direct support. The evidence does not disprove the connection either—it simply never looked.
| What was asked | What the evidence covers |
|---|---|
| FBN1 mutation → sciatica | FBN1 mutations → aortic root dilation, ectopia lentis, skeletal anomalies |
| Nerve root compression outcome | Cardiovascular, ocular, and skin-fibroblast outcomes |
My call: the hypothesis is biologically plausible but no study in this retrieval tested it. Confidence: not clear—the evidence gives no basis for a verdict either way.
Sources examined 31
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A Novel G to A Substitution at Nucleotide 1734 of the FBN1 Gene Predicting a C534Y Mutation Responsible for Marfan Syndrome
This study identifies a novel G to A substitution at nucleotide 1734 of the FBN1 gene, predicting a C534Y mutation that is responsible for Marfan Syndrome in a 30-year-old Caucasian male, providing insights into genetic diagnosis and potential therapeutic approaches.
DOI: 10.1159/000022867 -
Evaluating Japanese Patients With the Marfan Syndrome Using High-Throughput Microarray-Based Mutational Analysis of Fibrillin-1 Gene
This study evaluates the clinical characteristics and genetic mutations in Japanese patients with Marfan syndrome using a high-throughput microarray-based analysis of the fibrillin-1 gene, revealing a mutation detection rate of 71% and highlighting differences in phenotypic mani…
DOI: 10.1016/j.amjcard.2011.07.053 -
Role of fibrillin-1 genetic mutations and polymorphism in aortic dilatation in patients undergoing intracardiac repair of tetralogy of Fallot
This study investigates the prevalence of fibrillin-1 gene mutations and polymorphisms in patients with tetralogy of Fallot undergoing intracardiac repair, revealing a significant association between these genetic variants and aortic dilatation in the presence of abnormal aortic…
DOI: 10.1016/j.jtcvs.2007.12.044 -
Mutation screening of all 65 exons of the fibrillin-1 gene in 60 patients with Marfan syndrome: Report of 12 novel mutations
This study reports the mutation screening of all 65 exons of the fibrillin-1 gene in 60 patients with Marfan syndrome, identifying 12 novel mutations and providing insights into the mutation detection rates based on family structure.
DOI: 10.1002/(SICI)1098-1004(1997)10:4<280::AID-HUMU3>3.0.CO;2-L -
Missense mutations impair intracellular processing of fibrillin and microfibril assembly in Marfan syndrome
This study characterizes nine defined missense mutations in the fibrillin-1 (FBN1) gene from Marfan syndrome patients, showing that cysteine substitutions disrupt intracellular folding/transport and all mutant fibrillin molecules exhibit markedly reduced deposition into extracel…
DOI: 10.1093/hmg/2.12.2135 -
Exon 47 skipping of fibrillin-1 leads preferentially to cardiovascular defects in patients with thoracic aortic aneurysms and dissections
This study investigates the genotype-phenotype correlation of fibrillin-1 mutations in patients with thoracic aortic aneurysms and dissections, revealing that exon 47 skipping preferentially leads to cardiovascular defects, particularly in Chinese patients.
DOI: 10.1007/s00109-012-0931-y -
Clinical, pathological and molecular genetic findings in a case of neonatal Marfan syndrome
This study presents a case of neonatal Marfan syndrome in an infant who exhibited severe cardiovascular manifestations, including valve prolapse and a point mutation in the fibrillin 1 gene, ultimately leading to cardiac failure shortly after pacemaker implantation.
DOI: 10.1111/j.1651-2227.1999.tb01277.x -
Ophthalmic findings in a family with early-onset isolated ectopia lentis and the p.Arg62Cys mutation of the fibrillin-1 gene ( FBN1 )
This study describes the ophthalmic findings in a Chinese family with early-onset isolated ectopia lentis caused by the p.Arg62Cys mutation in the fibrillin-1 gene (FBN1), highlighting novel clinical manifestations including pupillary abnormalities and various types of glaucoma.
DOI: 10.3109/13816810.2012.718029 -
Mutation spectrum of the fibrillin‐1 ( FBN1 ) gene in Taiwanese patients with Marfan syndrome
This study establishes a national database of mutations in the fibrillin-1 (FBN1) gene associated with Marfan syndrome in Taiwanese patients, identifying 56 mutations in 62 of 157 families, with implications for genetic counseling and medical care.
DOI: 10.1111/j.1469-1809.2009.00545.x -
Fibrillin‐1 ( FBN1 ) gene frameshift mutations in Marfan patients: genotype–phenotype correlation
The study identifies four novel FBN1 frameshift mutations in Italian Marfan patients, links each mutation to distinct clinical features, and demonstrates that differing mutant mRNA expression levels may modulate phenotype severity, supporting a genotype–phenotype correlation inf…
DOI: 10.1034/J.1399-0004.2001.590610.X -
Denaturing HPLC-Identified Novel FBN1 Mutations, Polymorphisms, and Sequence Variants in Marfan Syndrome and Related Connective Tissue Disorders
This study utilizes denaturing high-performance liquid chromatography (DHPLC) to identify novel mutations and polymorphisms in the FBN1 gene associated with Marfan syndrome and related connective tissue disorders, achieving a high mutation detection rate compared to previous met…
DOI: 10.1089/gte.1997.1.237 -
The molecular genetics of Marfan syndrome and related disorders
A comprehensive 2006 review of Marfan syndrome and related fibrillin-based disorders, detailing FBN1 and FBN2 mutations, the role of microfibrils and TGF-beta signaling in pathogenesis, genotype–phenotype correlations, mouse and cell models, and implications for therapy (notably…
DOI: 10.1136/jmg.2005.039669 -
De-novo Williams–Beuren and inherited Marfan syndromes in a patient with developmental delay and lens dislocation
This study presents a case of a 6-year-old boy with developmental delay and lens dislocation, revealing a de-novo deletion associated with Williams-Beuren syndrome and a heterozygous mutation in the FBN1 gene linked to Marfan syndrome, highlighting the complex genetic interplay …
DOI: 10.1097/MCD.0000000000000180 -
Two novel mutations of <I>FBN1</I> gene in the patients with MFS among Han population
This study identifies two novel mutations in the FBN1 gene associated with Marfan syndrome in Han Chinese patients, contributing to the understanding of the genetic basis of the disease.
DOI: 10.3724/sp.j.1005.2010.00049 -
TGGE screening of the entire FBN1 coding sequence in 126 individuals with marfan syndrome and related fibrillinopathies
This study presents the results of temperature-gradient gel electrophoresis (TGGE) screening of the entire FBN1 coding sequence in 126 individuals with Marfan syndrome and related fibrillinopathies, identifying 53 mutations, including 33 novel ones, and discusses their implicati…
DOI: 10.1002/humu.10112 -
Phenotype–genotype correlation in a patient with co‐occurrence of Marfan and LEOPARD syndromes
This study reports a patient with both Marfan syndrome and LEOPARD syndrome, identifying novel mutations in the FBN1 and PTPN11 genes that contribute independently to the patient's clinical features.
DOI: 10.1002/ajmg.a.32735 -
Double heterozygous variants in FBN1 and FBN2 in a Thai woman with Marfan and Beals syndromes
A living Thai patient with combined Marfan syndrome (MFS) and Beals syndrome (BS) carries double heterozygous mutations in FBN1 and FBN2, with FBN1 p.Cys1053Trp being de novo and FBN2 p.Gly880Ser inherited from the mother, supported by sequencing and in silico structural analyse…
DOI: 10.1016/j.ejmg.2020.103982 -
Recessive Mutations in LEPREL1 Underlie a Recognizable Lens Subluxation Phenotype
This study identifies a novel homozygous LEPREL1 mutation in four sisters from a consanguineous Saudi family with non-syndromic lens subluxation and juvenile cataract, linking LEPREL1 loss-of-function to a recognizable ocular phenotype and expanding the differential diagnosis of…
DOI: 10.3109/13816810.2014.985847 -
Classic, atypically severe and neonatal Marfan syndrome: twelve mutations and genotype–phenotype correlations in FBN1 exons 24–40
This study identifies twelve mutations in the FBN1 gene associated with classic, atypically severe, and neonatal Marfan syndrome, enhancing the understanding of genotype-phenotype correlations.
DOI: 10.1038/sj.ejhg.5200582 -
A Marfan syndrome gene expression phenotype in cultured skin fibroblasts
Cultured human skin fibroblasts from Marfan syndrome patients with FBN1 mutations show a distinct gene expression phenotype versus controls, including downregulation of elastin and certain collagens and altered TGF-beta–related genes, validated by qRT-PCR and replicated in an in…
DOI: 10.1186/1471-2164-8-319 -
Qualitative and quantitative analysis of FBN1 mRNA from 16 patients with Marfan Syndrome
This study investigates the qualitative and quantitative effects of 16 mutations in the FBN1 gene on mRNA levels in fibroblasts from patients with Marfan Syndrome, revealing significant variability in expression levels and the impact of specific mutations on splicing and transcr…
DOI: 10.1186/s12881-015-0260-4 -
Observations on the Etiology of Trigeminal Neuralgia, Hemifacial Spasm, Acoustic Nerve Dysfunction and Glossopharyngeal Neuralgia. Definitive Microsurgical Treatment and Results in 117 Patients
A landmark case-series demonstrating that vascular cross-compression at cranial nerve root entry/exit zones underlies trigeminal neuralgia, hemifacial spasm, acoustic nerve dysfunction, and glossopharyngeal neuralgia, with relief achieved by microsurgical decompression in 117 pa…
DOI: 10.1055/s-0028-1090369 -
Epigenetic Gene Silencing Underlies C-Fiber Dysfunctions in Neuropathic Pain
Nerve injury triggers REST/NRSF-mediated epigenetic silencing of mu opioid receptor and Na_v1.8 in dorsal root ganglion neurons, causing C-fiber dysfunction and loss of peripheral morphine analgesia, which can be reversed by NRSF knockdown.
DOI: 10.1523/jneurosci.5541-09.2010 -
Reconstruction of reflex pathways to the atonic bladder after conus medullaris injury: Preliminary clinical results
This study investigates the effectiveness of spinal root anastomoses in restoring bladder function in 10 paraplegic patients with conus medullaris injury, resulting in 70% of patients regaining satisfactory bladder control within 18-24 months post-surgery.
DOI: 10.1002/micr.20504 -
An animal model for the neuromodulation of neurogenic bladder dysfunction
This study establishes a rat model of neurogenic bladder after complete spinal cord transection and demonstrates that chronic sacral nerve root electrostimulation reduces bladder hyperreflexia compared with sham stimulation.
DOI: 10.1046/j.1464-410x.1998.00676.x -
Changes of Bioelectric Activity of the Brain of Patients with Different Types of Somatic Dysfunction during the Implementation of a Myofascial Release
Brain EEG connectivity changes during myofascial release differ by somatic dysfunction status, with healthy controls showing overall increases in interregional EEG connectivity while patients exhibit region-specific alterations depending on the treated site.
DOI: 10.32885/2220-0975-2015-3-4-13-20 -
The Nerve Root Entry Zone Is Highly Vulnerable to Intrathecal Tetracaine in Rabbits
This study investigates the morphological changes in nerve fibers at the nerve root entry zone in rabbits after intrathecal administration of varying concentrations of tetracaine, revealing that oligodendrocyte myelin sheaths are particularly vulnerable to high doses of this loc…
DOI: 10.1213/01.ANE.0000153018.90619.65 -
Normal proprioceptive trigeminal afferents in patients with Sjögren's syndrome and sensory neuronopathy
In a small electrophysiological study of humans, the authors show that Sjogren's syndrome–associated pure sensory neuropathy involves selective dysfunction of gasserian (trigeminal) ganglion neurons with preserved jaw-jerk reflex, distinguishing it from trigeminal sensory–motor …
DOI: 10.1002/ANA.410280609 -
Axotomy differentially regulates voltage-gated calcium currents in mice sensory neurones
This study shows that five days after sciatic nerve axotomy in adult mice, dorsal root ganglion neurons display heterogeneous, axotomy-dependent changes in low- (T-type) and high-voltage-activated calcium currents across three electrophysiological subtypes, implying differential…
DOI: 10.1097/00001756-200301200-00027 -
Bone marrow-derived TNF-α causes diabetic neuropathy in mice
Bone marrow–derived TNF-α, particularly from proinsulin-producing BM-derived cells (PI-BMDCs), drives diabetic neuropathy in STZ-diabetic mice; selective loss of TNF-α in BM or specifically in PI-BMDCs prevents nerve dysfunction and neuronal apoptosis, implicating PI-BMDC–derive…
DOI: 10.1007/s00125-014-3440-4 -
Diabetic neuropathy
This Nature Reviews Neurology Primer provides a comprehensive synthesis of diabetic neuropathy, detailing its epidemiology, pathophysiology, diagnostic approaches, prevention, and current and emerging treatments, with emphasis on metabolic, vascular, and insulin-signaling disrup…
DOI: 10.1038/s41572-019-0092-1