The N355K atlastin 1 mutation is associated with hereditary sensory neuropathy and pyramidal tract features

Leonardis, Lea; Auer‐Grumbach, Michaela; Papić, Lea; Zidar, Janez

doi:10.1111/j.1468-1331.2012.03665.x

Cited by 15 publications

(12 citation statements)

References 33 publications

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“…Asymptomatic individuals were also included, but excluded from the analysis of AAO and pure or complicated form. Patients with elderly sensory neuropathy caused by ATL1 gene mutations were excluded in this study [57, 58]. We reanalysed the clinical and genetic data in ATL1 gene mutant patients and performed a correlation analysis of AAO with mutational class in ATL1 gene.…”

Section: Methodsmentioning

confidence: 99%

Clinical features and genotype-phenotype correlation analysis in patients with ATL1 mutations: A literature reanalysis

Zhao

Liu

2017

Transl Neurodegener

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BackgroundThe hereditary spastic paraplegias (HSPs) are a group of clinically and genetically heterogeneous disorders. Approximately 10% of the autosomal dominant (AD) HSPs (ADHSPs) have the spastic paraplegia 3A (SPG3A) genotype which is caused by ATL1 gene mutations. Currently there are more than 60 reported ATL1 gene mutations and the genotype-phenotype correlation remains unclear. The study aims to investigate the genotype-phenotype correlation in SPG3A patients.MethodsWe performed a reanalysis of the clinical features and genotype-phenotype correlations in 51 reported studies exhibiting an ATL1 gene mutation.ResultsMost HSPs-SPG3A patients exhibited an early age at onset (AAO) of <10 years old, and showed an autosomal dominant pure spastic paraplegia. We found that 14% of the HSPs-SPG3A patients presented complicated phenotypes, with distal atrophy being the most common complicated symptom. The AAO of each mutation group was not statistically significant (P > 0.05). The mutational spectrum associated with ATL1 gene mutation is wide, and most mutations are missense mutations, but do not involve the functional motif of ATL1 gene encoded atlastin-1 protein.ConclusionsOur findings indicate that there is no clear genotype-phenotype correlation in HSPs-SPG3A patients. We also find that exons 4, 7, 8 and 12 are mutation hotspots in ATL1 gene.Electronic supplementary materialThe online version of this article (doi:10.1186/s40035-017-0079-3) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Clinical features and genotype-phenotype correlation analysis in patients with ATL1 mutations: A literature reanalysis

Zhao

Liu

2017

Transl Neurodegener

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“…Nonetheless, motor involvement in sensory neuropathies is not limited to HSAN type II since it has been reported in HSAN type I, such as SPTLC1, SPTLC2, RAB7, or ATL1 related neuropathies. [10][11][12] Our group of patients illustrates well the phenotypic variability associated to FAM134B gene mutations, even within the same family, with distinctive sensory impairment severity, motor and autonomic dysfunction. Recurrent ulcerations due to nociception impairment complicated with osteomyelitis and osteonecrosis were frequent as previously reported.…”

Section: Discussionmentioning

confidence: 56%

“…The pathophysiological mechanism for the motor impairment and the reduction of compound motor action amplitudes seen in patients carrying FAM134B mutations remains to be elucidated. Nonetheless, motor involvement in sensory neuropathies is not limited to HSAN type II since it has been reported in HSAN type I, such as SPTLC1 , SPTLC2 , RAB7 , or ATL1 related neuropathies …”

Section: Discussionmentioning

confidence: 99%

Hereditary sensory autonomic neuropathy type II: Report of two novel mutations in the FAM134B gene

Campos

Vidailhet

Toutain

et al. 2019

J Peripheral Nervous Sys

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Hereditary sensory autonomic neuropathy (HSAN) type II is a rare, autosomal recessive, and early onset sensory neuropathy, characterized by severe and progressive sensation impairment, leading to ulcero‐mutilating complications. FAM134B gene, also known as RETREG1 gene, mutations have been reported to be associated to HSAN‐IIB. We report four patients from two unrelated families who developed during childhood a sensory axonal neuropathy with variable severity and pronounced nociception impairment. Complications such as recurrent ulcerations, osteomyelitis, and osteonecrosis leading to distal amputation were noticed. Dysautonomia was mild or even absent in our group of patients. Additionally, either clinical or neurophysiological motor impairment was not uncommon. Presence of upper motor neuron signs was also a distinctive feature in two related patients. After extensive workup, two novel homozygous mutations in the FAM134B gene were identified. This report expands the clinical and genetic spectrum of HSAN type II and emphasizes the phenotype variability even within the same family.

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“…The causality of these two variants (c.1039A˃C and c.1064A˃T) is strengthened by their presence in guanylate‐binding protein domain, C‐terminal. Moreover, the missense pathogenic variant in the neighbouring nucleotide within the same triplet were reported previously in both variants, p.Met347Ile in SPG3 patient (Al‐Maawali et al., ; Leonardi et al., ) and p.Asn355Cys in a patient with hereditary sensory neuropathy (Guelly et al., ; Leonardis et al., ). Two of the revealed variants (c.916A˃G and c.505A˃G) were subsequently found in the patient's unaffected parent, which raises doubts about the pathogenicity.…”

Section: Discussionmentioning

confidence: 60%

“…To date, more than 50 pathogenic/likely pathogenic variants (mainly missense, rarely splice and frame‐shift mutation, no nonsense) and only one gross deletion have been described in the ATL1 gene (Sulek et al., ). Variants in the ATL1 gene have been described not only in spastic paraplegia but also rarely in very variable phenotypes, in patients with axonal motor neuropathy (Fusco et al., ; Al‐Maawali et al., ; Leonardis et al., ) and hereditary sensory neuropathy (Guelly et al., ). According to the population databases ExAC (http://exac.broadinstitute.org/) and the Exome Variant Server (EVS) (http://evs.gs.washington.edu), a few benign missense polymorphisms also exist in this gene in the healthy population.…”

Section: Introductionmentioning

confidence: 99%

Disease‐Causing Variants in the ATL1 Gene Are a Rare Cause of Hereditary Spastic Paraplegia among Czech Patients

Meszarosova

Grečmalová

Brazdilova

et al. 2017

Annals of Human Genetics

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Variants in the ATL1 gene have been repeatedly described as the second most frequent cause of hereditary spastic paraplegia (HSP), a motor neuron disease manifested by progressive lower limb spasticity and weakness. Variants in ATL1 have been described mainly in patients with early onset HSP. We performed Sanger sequencing of all coding exons and adjacent intron regions of the ALT1 gene in 111 Czech patients with pure form of HSP and additional Multiplex-Ligation Probe Analysis (MLPA) testing targeting the ATL1 gene in 56 of them. All patients except seven were previously tested by Sanger sequencing of the SPAST gene with negative results. ATL1 diagnostic testing revealed only five missense variants in the ATL1 gene. Four of them are novel, but we suppose only two of them to be pathogenic and causal. The remaining variants are assumed to be benign. MLPA testing in 56 of sequence variant negative patients revealed no gross deletion in the ATL1 gene. Variants in the ATL1 gene are more frequent in patients with early onset HSP, but in general the occurrence of pathogenic variants in the ATL1 gene is low in our cohort, less than 4.5% and less than 11.1% in patients with onset before the age of ten. Variants in the ATL1 gene are a less frequent cause of HSP among Czech patients than has been previously reported among other populations.

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The N355K atlastin 1 mutation is associated with hereditary sensory neuropathy and pyramidal tract features

Cited by 15 publications

References 33 publications

Clinical features and genotype-phenotype correlation analysis in patients with ATL1 mutations: A literature reanalysis

Clinical features and genotype-phenotype correlation analysis in patients with ATL1 mutations: A literature reanalysis

Hereditary sensory autonomic neuropathy type II: Report of two novel mutations in the FAM134B gene

Disease‐Causing Variants in the ATL1 Gene Are a Rare Cause of Hereditary Spastic Paraplegia among Czech Patients

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