Hereditary motor neuron disease in a large Norwegian family with a “H46R” substitution in the superoxide dismutase 1 gene

Østern, Rune; Fagerheim, Toril; Ørstavik, Kristin; Holmøy, Trygve; Heiberg, Arvid; Lund-Petersen, Inger; Strom, Tim M.; Nilssen, Øivind; Dahl, Arve

doi:10.1016/j.nmd.2012.01.011

Cited by 13 publications

(10 citation statements)

References 33 publications

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“…Subclinical sensory involvement was observed as low SNAP values in one-fourth of patients. This asymptomatic electrophysiological sensory involvement is similar to that found in sporadic ALS [11] and FALS with H46R mutation in SOD1 gene [12] but appears to be less marked than the sensory involvement in Kennedy's disease patients [13]. Because comorbidities such as diabetes are quite common in the age group of LOSMoN patients, more patients need to be carefully investigated by laboratory and electrophysiological examinations to fully define the extent and significance of primary sensory involvement in LOSMoN.…”

Section: Discussionsupporting

confidence: 66%

Late-onset spinal motor neuronopathy – A common form of dominant SMA

Penttilä

Jokela

Huovinen

et al. 2014

Neuromuscular Disorders

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Section: Discussionsupporting

confidence: 66%

Late-onset spinal motor neuronopathy – A common form of dominant SMA

Penttilä

Jokela

Huovinen

et al. 2014

Neuromuscular Disorders

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“…The families were previously tested for the PMP22 duplication by real-time quantitative PCR and point mutations in PMP22 , GJB1 , MPZ , LITAF , MFN2 , and EGR2 by conventional Sanger sequencing [2]. Later, a duplication of MPZ was identified in one CMT family, and another CMT family had a point mutation in the SOD1 gene [14, 19]. A mutation was identified in 22 CMT families.…”

Section: Methodsmentioning

confidence: 99%

Genetic Diagnosis of Charcot-Marie-Tooth Disease in a Population by Next-Generation Sequencing

Høyer

Braathen

Busk

et al. 2014

BioMed Research International

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Charcot-Marie-Tooth (CMT) disease is the most prevalent inherited neuropathy. Today more than 40 CMT genes have been identified. Diagnosing heterogeneous diseases by conventional Sanger sequencing is time consuming and expensive. Thus, more efficient and less costly methods are needed in clinical diagnostics. We included a population based sample of 81 CMT families. Gene mutations had previously been identified in 22 families; the remaining 59 families were analysed by next-generation sequencing. Thirty-two CMT genes and 19 genes causing other inherited neuropathies were included in a custom panel. Variants were classified into five pathogenicity classes by genotype-phenotype correlations and bioinformatics tools. Gene mutations, classified certainly or likely pathogenic, were identified in 37 (46%) of the 81 families. Point mutations in known CMT genes were identified in 21 families (26%), whereas four families (5%) had point mutations in other neuropathy genes, ARHGEF10, POLG, SETX, and SOD1. Eleven families (14%) carried the PMP22 duplication and one family carried a MPZ duplication (1%). Most mutations were identified not only in known CMT genes but also in other neuropathy genes, emphasising that genetic analysis should not be restricted to CMT genes only. Next-generation sequencing is a cost-effective tool in diagnosis of CMT improving diagnostic precision and time efficiency.

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“…Therefore, it was proposed to be a unique mutation in the Asian population. However, the mutation has been reported in one USA (12), one French (13), two German (14,15) and three Norwegian (16)(17)(18) pedigrees, suggesting that it also exists in ALS patients of European descent. Although considerable inter-and intra-family variations exist regarding age of onset and disease duration, all patients with the p.H46R mutation unexceptionally had a lower limbs onset and very slow progression; the interval between the presentation of symptoms and respiratory failure usually exceeds 10 years (Table I), with the longest survival of 51 years (16).…”

Section: Discussionmentioning

confidence: 99%

“…However, the mutation has been reported in one USA (12), one French (13), two German (14,15) and three Norwegian (16)(17)(18) pedigrees, suggesting that it also exists in ALS patients of European descent. Although considerable inter-and intra-family variations exist regarding age of onset and disease duration, all patients with the p.H46R mutation unexceptionally had a lower limbs onset and very slow progression; the interval between the presentation of symptoms and respiratory failure usually exceeds 10 years (Table I), with the longest survival of 51 years (16). Most of the patients manifested with a pure lower motor neuron disease without bulbar involvement, therefore they are easily misdiagnosed as hereditary peripheral neuropathy before a final diagnosis of ALS is made (13,(16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

“…Although considerable inter-and intra-family variations exist regarding age of onset and disease duration, all patients with the p.H46R mutation unexceptionally had a lower limbs onset and very slow progression; the interval between the presentation of symptoms and respiratory failure usually exceeds 10 years (Table I), with the longest survival of 51 years (16). Most of the patients manifested with a pure lower motor neuron disease without bulbar involvement, therefore they are easily misdiagnosed as hereditary peripheral neuropathy before a final diagnosis of ALS is made (13,(16)(17)(18). These findings indicate that the p.H46R mutation is associated with a specific phenotype, i.e.…”

Section: Discussionmentioning

confidence: 99%

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H46R SOD1 mutation is consistently associated with a relatively benign form of amyotrophic lateral sclerosis with slow progression

Zou

Liu

2016

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by progressive loss of motor neurons in the motor cortex, brainstem, and spinal cord. Over 60% of patients die from respiratory failure within three years of presentation. We report two ALS patients carrying the p.H46R missense mutation in the SOD1 gene presented with a characteristic clinical phenotype of very slow progression. We also reviewed the 13 pedigrees harbouring the p.H46R mutation reported previously. SOD1 p.H46R mutation is consistently associated with a specific phenotype, i.e. lower limb onset with rare bulbar involvement, and a slow progression with longer survival. It is important to recognize the typical clinical picture of the SOD1 p.H46R mutation, and SOD1 sequencing may be necessary to give the patient correct diagnosis and prognosis.

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Hereditary motor neuron disease in a large Norwegian family with a “H46R” substitution in the superoxide dismutase 1 gene

Cited by 13 publications

References 33 publications

Late-onset spinal motor neuronopathy – A common form of dominant SMA

Late-onset spinal motor neuronopathy – A common form of dominant SMA

Genetic Diagnosis of Charcot-Marie-Tooth Disease in a Population by Next-Generation Sequencing

H46R SOD1 mutation is consistently associated with a relatively benign form of amyotrophic lateral sclerosis with slow progression

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