A new form of congenital proprioceptive sensory neuropathy associated with arthrogryposis multiplex

Shibasaki, Hiroshi; Hitomi, Takefumi; Mezaki, Takahiro; Kihara, Takeshi; Tomimoto, Hidekazu; Ikeda, Akio; Shimohama, Shun; Ito, Masako; Oka, Nobuyuki

doi:10.1007/s00415-004-0539-4

Cited by 9 publications

(6 citation statements)

References 15 publications

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“…We tested the H reflex in the tibial nerves of 13-week-old Swl/ϩ mutants and WT littermate mice. The H reflex, which measures the latency over the monosynaptic reflex arc through the afferent Ia fibers and efferent ␣-motor fibers, primarily represents proprioceptive function (Shibasaki et al, 2004). Strikingly, the H reflex was not detectable in the hindlimbs of any of the Swl/ϩ mice examined (n ϭ 8), but it was present in all WT mice (n ϭ 6) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Proprioceptive Sensory Neuropathy in Mice with a Mutation in the Cytoplasmic Dynein Heavy Chain 1 Gene

Chen¹,

Levedakou²,

Millen³

et al. 2007

J. Neurosci.

151

163

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Mice heterozygous for the radiation-induced Sprawling (Swl) mutation display an early-onset sensory neuropathy with muscle spindle deficiency. The lack of an H reflex despite normal motor nerve function in the hindlimbs of these mutants strongly suggests defective proprioception. Immunohistochemical analyses reveal that proprioceptive sensory neurons are severely compromised in the lumbar dorsal root ganglia of newborn Swl/ϩ mice, whereas motor neuron numbers remain unaltered even in aged animals. We have used positional cloning to identify a nine base-pair deletion in the cytoplasmic dynein heavy chain 1 gene (Dync1h1) in this mutant. Furthermore, we demonstrate that Loa/ϩ mice, which have previously been shown to carry a missense point mutation in Dync1h1 that results in late-onset motor neuron loss, also present with a severe, early-onset proprioceptive sensory neuropathy. Interestingly, in contrast to the Loa mutation, the Swl mutation does not delay disease progression in a motor neuron disease mouse model overexpressing a human mutant superoxide dismutase (SOD1 G93A ) transgene. Together, we provide in vivo evidence that distinct mutations in cytoplasmic dynein can either result in a pure sensory neuropathy or in a sensory neuropathy with motor neuron involvement.

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Section: Resultsmentioning

confidence: 99%

Proprioceptive Sensory Neuropathy in Mice with a Mutation in the Cytoplasmic Dynein Heavy Chain 1 Gene

Chen¹,

Levedakou²,

Millen³

et al. 2007

J. Neurosci.

151

163

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“…Global loss of PIP5K1C in humans causes lethal congenital contractural syndrome type 3, 23 a syndrome featuring severe arthrogryposis (joint contractures) and death shortly before or immediately after birth. Joint contractures are seen in other human disorders that impair proprioception, 24 including biallelic loss of PIEZO2. 25 – 27 The proprioceptive deficits that we observed in Advil-Cre × Pip5k1c fl/ fl mice might relate to developmental loss of Pip5k1c in DRG, depletion of PIP 2 , and/or impaired neurotrophin-mediated neurite outgrowth.…”

Section: Discussionmentioning

confidence: 99%

Conditional deletion of Pip5k1c in sensory ganglia and effects on nociception and inflammatory sensitization

Loo

Zylka

2017

Mol Pain

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Phosphatidylinositol 4-phosphate 5-kinase type 1 gamma (Pip5k1c) generates phosphatidylinositol 4,5-bisphosphate, also known as PI(4,5)P2 or PIP2. Many pronociceptive signaling pathways and receptor tyrosine kinases signal via PIP2 hydrolysis. Previously, we found that pain signaling and pain sensitization were reduced in Pip5k1c+/− global heterozygous knockout mice. Here, we sought to evaluate the extent to which dorsal root ganglia selective deletion of Pip5k1c affected nociception in mice. Initially, we crossed sensory neuron-selective Advillin-Cre mice with a conditional Pip5k1c knockout (cKO) allele (Pip5k1cfl/fl). However, these mice displayed an early onset proprioceptive deficit. To bypass this early onset phenotype, we used two different tamoxifen-inducible Cre lines (Brn3a-Cre-ERT2 and Advillin-Cre-ERT2) to conditionally delete Pip5k1c in adults. Tamoxifen induced high efficiency deletion of PIP5K1C in dorsal root ganglia and slightly reduced PIP5K1C in spinal cord and brain in Brn3a-Cre-ERT2 × Pip5k1cfl/fl (Brn3a cKO) mice while PIP5K1C was selectively deleted in dorsal root ganglia with no changes in spinal cord or brain in Advillin-Cre-ERT2 × Pip5k1cfl/fl (Advil cKO) mice. Acute thermosensation and mechanosensation were not altered in either line relative to wild-type mice. However, thermal hypersensitivity and mechanical allodynia recovered more rapidly in Brn3a cKO mice, but not Advil cKO mice, following hind paw inflammation. These data collectively suggest that PIP5K1C regulates nociceptive sensitization in more regions of the nervous system than dorsal root ganglia alone.

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“…[24][25][26][27] Arthrogryposis can also arise from a defect within the nervous system including structural/functional brain and spinal cord anomalies, motor neuron dysfunction, peripheral neuropathies, impaired axoglial function, hypomyelination, neuromuscular junction dysfunction, channelopathies, intrinsic muscle disorders, and central, peripheral, or mixed central/peripheral hypotonia. 7,9,[28][29][30][31][32][33][34][35][36][37] The diagnosis of these cases can be delineated based on a detailed neurological examination, Figure 2 presents an algorithm to inform clinicians' options and investigations that should be considered when a concern for AMC is identified. Table 1.…”

Section: Classificationmentioning

confidence: 99%

Fetal arthrogryposis multiplex congenita/fetal akinesia deformation sequence (FADS)—Aetiology, diagnosis, and management

et al. 2019

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Arthrogryposis multiplex congenita (AMC) refers to an aetiologically heterogenous condition, which consists of joint contractures affecting two or more joints starting prenatally. The incidence is approximately one in 3000 live births; however, the prenatal incidence is higher, indicating a high intrauterine mortality. Over 320 genes have been implicated showing the genetic heterogeneity of the condition. AMC can be of extrinsic aetiology resulting from intrauterine crowding secondary to congenital structural uterine abnormalities (eg, bicornuate or septate uterus), uterine tumors (eg, fibroid), or multifetal pregnancy or intrinsic/primary/fetal aetiology, due to functional abnormalities in the brain, spinal cord, peripheral nerves, neuromuscular junction, muscles, bones, restrictive dermopathies, tendons and joints. Unlike many of the intrinsic/primary/fetal causes which are difficult to treat, secondary AMC can be treated by physiotherapy with good response. Primary cases may present prenatally with fetal akinesia associated with joint contractures and occasionally brain abnormalities, decreased muscle bulk, polyhydramnios, and nonvertex presentation while the secondary cases usually present with isolated contractures. Complete prenatal and postnatal investigations are needed to identify an underlying aetiology and provide information regarding its prognosis and inheritance, which is critical for the obstetrical care providers and families to optimize the pregnancy management and address future reproductive plans.

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A new form of congenital proprioceptive sensory neuropathy associated with arthrogryposis multiplex

Cited by 9 publications

References 15 publications

Proprioceptive Sensory Neuropathy in Mice with a Mutation in the Cytoplasmic Dynein Heavy Chain 1 Gene

Proprioceptive Sensory Neuropathy in Mice with a Mutation in the Cytoplasmic Dynein Heavy Chain 1 Gene

Conditional deletion of Pip5k1c in sensory ganglia and effects on nociception and inflammatory sensitization

Fetal arthrogryposis multiplex congenita/fetal akinesia deformation sequence (FADS)—Aetiology, diagnosis, and management

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