A mild case of giant axonal neuropathy without central nervous system manifestation

Koichihara, Reiko; Saito, Takashi; Ishiyama, Akihiko; Komaki, Hirofumi; Yuasa, Shota; Saito, Yoshiaki; Nakagawa, Eiji; Sugai, Kenji; Shiihara, Takashi; Shioya, Ayako; Saito, Yuko; Higuchi, Yujiro; Hashiguchi, Akihiro; Takashima, Hiroshi; Sasaki, Masayuki

doi:10.1016/j.braindev.2015.09.001

Cited by 11 publications

(7 citation statements)

References 9 publications

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“…The most commonly reported electrodiagnostic and neuroimaging findings in GAN include sensorimotor neuropathy and nonspecific supra and infratentorial white matter signal changes, respectively. Regarding imaging and electrophysiologic findings, our patients were similar to reported features as well (Aharoni et al, 2016; Almeida et al, 2016; Garg et al, 2018; Koichihara et al, 2016; Mohammad et al, 2014). Although ocular abnormalities such as optic atrophy (Bacquet et al, 2018), retinitis pigmentosa (Kamate et al, 2014), ptosis, and nystagmus (Vijaykumar et al, 2015) are frequently reported in GAN, but only photosensitivity and the history of corneal ulcer were detected in patient 1.…”

Section: Discussionsupporting

confidence: 88%

Expanding the genetic spectrum of giant axonal neuropathy: Two novel variants in Iranian families

Ashrafi

Dehnavi

Tavasoli

et al. 2023

Molec Gen & Gen Med

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Background Giant axonal neuropathy (GAN) is a progressive childhood hereditary polyneuropathy that affects both the peripheral and central nervous systems. Disease‐causing variants in the gigaxonin gene (GAN) cause autosomal recessive giant axonal neuropathy. Facial weakness, nystagmus, scoliosis, kinky or curly hair, pyramidal and cerebellar signs, and sensory and motor axonal neuropathy are the main symptoms of this disorder. Here, we report two novel variants in the GAN gene from two unrelated Iranian families. Methods Clinical and imaging data of patients were recorded and evaluated, retrospectively. Whole‐exome sequencing (WES) was undertaken in order to detect disease‐causing variants in participants. Confirmation of a causative variant in all three patients and their parents was carried out using Sanger sequencing and segregation analysis. In addition, for comparing to our cases, we reviewed all relevant clinical data of previously published cases of GAN between the years 2013–2020. Results Three patients from two unrelated families were included. Using WES, we identified a novel nonsense variant [NM_022041.3:c.1162del (p.Leu388Ter)], in a 7‐year‐old boy of family 1, and a likely pathogenic missense variant [NM_022041.3:c.370T>A (p.Phe124Ile)], in two affected siblings of the family 2. Clinical examination revealed typical features of GAN‐1 in all three patients, including walking difficulties, ataxic gait, kinky hair, sensory‐motor polyneuropathy, and nonspecific neuroimaging abnormalities. Review of 63 previously reported cases of GAN indicated unique kinky hair, gait problem, hyporeflexia/areflexia, and sensory impairment were the most commonly reported clinical features. Conclusions One homozygous nonsense variant and one homozygous missense variant in the GAN gene were discovered for the first time in two unrelated Iranian families that expand the mutation spectrum of GAN. Imaging findings are nonspecific, but the electrophysiological study in addition to history is helpful to achieve the diagnosis. The molecular test confirms the diagnosis.

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Section: Discussionsupporting

confidence: 88%

Expanding the genetic spectrum of giant axonal neuropathy: Two novel variants in Iranian families

Ashrafi

Dehnavi

Tavasoli

et al. 2023

Molec Gen & Gen Med

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“…Patient 3 has missense heterozygous mutations, one of which has been recently reported as pathogenic in a patient with GAN. [ 6 ] In view of strong clinical suspicion and the fact that parents are carriers of these mutations, it is likely that the other mutation is a novel missense mutation for GAN.…”

Section: R Esultsmentioning

confidence: 99%

Giant axonal neuropathy: Clinical, radiological, and genetic features

Garg

Kulkarni

Hegde

et al. 2018

Ann Indian Acad Neurol

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“…Specifically, gigaxonin plays an important role in the breakdown of neurofilament (NF) [ 8 ], where the cellular hallmark of GAN pathology is the formation of its large aggregates [ 2 , 3 , 5 ]. According to the Leiden Open Variation Database (LOVD) (updated 2022), National Center for Biotechnology Information (NCBI) (updated 2022), and the mutation summary reported by Lescouzères and Bomont, P. (2020), there are 89 variants that lead to manifestation of GAN ( Figure 1 ) [ 5 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic Approaches for the Treatment of Giant Axonal Neuropathy

Shirakaki

Roshmi

Yokota

2022

JPM

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Giant axonal neuropathy (GAN) is a pediatric, hereditary, neurodegenerative disorder that affects both the central and peripheral nervous systems. It is caused by mutations in the GAN gene, which codes for the gigaxonin protein. Gigaxonin plays a role in intermediate filament (IF) turnover hence loss of function of this protein leads to IF aggregates in various types of cells. These aggregates can lead to abnormal cellular function that manifests as a diverse set of symptoms in persons with GAN including nerve degeneration, cognitive issues, skin diseases, vision loss, and muscle weakness. GAN has no cure at this time. Currently, an adeno-associated virus (AAV) 9-mediated gene replacement therapy is being tested in a phase I clinical trial for the treatment of GAN. This review paper aims to provide an overview of giant axonal neuropathy and the current efforts at developing a treatment for this devastating disease.

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A mild case of giant axonal neuropathy without central nervous system manifestation

Cited by 11 publications

References 9 publications

Expanding the genetic spectrum of giant axonal neuropathy: Two novel variants in Iranian families

Expanding the genetic spectrum of giant axonal neuropathy: Two novel variants in Iranian families

Giant axonal neuropathy: Clinical, radiological, and genetic features

Genetic Approaches for the Treatment of Giant Axonal Neuropathy

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