Unusual upper limb features in <i>SORD</i> neuropathy

Record, Christopher J; Pipis, Menelaos; Blake, Julian; Currò, Riccardo; Lunn, Michael P.; Rossor, Alexander M.; Laurá, Matilde; Cortese, Andrea; Reilly, Mary M.

doi:10.1111/jns.12492

Cited by 6 publications

(5 citation statements)

References 5 publications

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“…The characteristics of SORD-related CMT have been typically described as a length-dependent neuropathy, characterized by distal hereditary motor neuropathy (dHMN) or a predominantly motor presentation resembling CMT2. Unusual features were also observed, including mild hearing loss, dermographism, brisk re exes, denervation, conduction block, and small ber impairment on EMG [9,17]. This may be attributed to diabetic mononeuropathy caused by high sorbitol levels involved in the pathogenesis.…”

Section: Discussionmentioning

confidence: 97%

“…Here, we also summarized all the SORD mutations reported in 13 previous literatures (Table 1). A total of 101cases with 18 mutations were reported [4,[9][10][11][12][13][14][15][16][17][18][19][20]. Among these, 73 patients carried the homozygous deletion variant c.757delG (p.A253Qfs*27), 27 cases in a compound heterozygous state of combination of c.757delG with another variant, one patient harboring a compound heterozygous variants of c.404A > G and c.908þ1G > C. Most of the variants in SORD are frameshift or splicing variants.…”

Section: Genetic Datamentioning

confidence: 99%

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A novel mutation in SORD gene associated with Distal Hereditary Motor Neuropathies

Yuan,

Zhang,

Shang

et al. 2023

Preprint

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Background Distal hereditary motor neuropathy (dHMN) is a heterogeneous group of hereditary diseases caused by the gradual degeneration of the lower motor neuron. More than 30 genes associated with dHMN have been reported, while 70–80% of those with the condition are still unable to receive a genetic diagnosis. Methods A 26-year-old man experiencing gradual weakness in his lower limbs was referred to our hospital, and data on clinical features, laboratory tests, and electrophysiological tests were collected. To identify the disease-causing mutation, we conducted whole exome sequencing (WES) and then validated it through Sanger sequencing for the proband and his parents. Silico analysis was performed to predict the pathogenesis of the identified mutations. A literature review of all reported mutations of the related gene for the disease was performed. Results The patient presented with dHMN phenotype harboring a novel homozygous variant c.361G > C (p.Ala121Pro) in SORD, inherited from his parents, respectively. A121 is a highly conserved site and A121P is predicted to disrupt its normal splicing. A total of 13 published articles including 101 patients reported 18 SORD variants. Almost all described cases have the homozygous deletion variant c.757delG (p.A253Qfs*27) or compound heterozygous state of a combination of c.757delG (p.A253Qfs*27) with another variant. The variant c.361G > C (p.Ala121Pro) detected in our patient was the second homozygous variant in SORD-associated hereditary neuropathy. Conclusion One novel homozygous variant c.361G > C (p.Ala121Pro) in SORD was identified in a Chinese patient with dHMN phenotype, which expands the mutation spectrum of SORD-associated hereditary neuropathy and underscores the significance of screening for SORD variants in patients with undiagnosed hereditary neuropathy patients.

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Section: Discussionmentioning

confidence: 97%

Section: Genetic Datamentioning

confidence: 99%

A novel mutation in SORD gene associated with Distal Hereditary Motor Neuropathies

Yuan,

Zhang,

Shang

et al. 2023

Preprint

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show abstract

“…The characteristics of SORD-related CMT have been typically described as a length-dependent neuropathy, characterized by distal hereditary motor neuropathy (dHMN) or a predominantly motor presentation resembling CMT2. Unusual features were also observed, including mild hearing loss, dermographism, brisk reflexes, denervation, conduction block, and small fiber impairment on EMG [ 8 , 26 ]. This may be attributed to diabetic mononeuropathy caused by high sorbitol levels involved in the pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we also summarized all the SORD mutations reported in previous literatures (Table 2). A total of 101cases with 18 mutations were reported [4,8,[19][20][21][22][23][24][25][26][27][28][29]. Among these, 73 patients carried the homozygous deletion variant c.757delG (p.A253Qfs*27), 27 cases in a compound heterozygous state of combination of c.757delG with another variant, one patient harboring a compound heterozygous variants of c.404 A > G and c.908 + 1G > C. Most of the variants in SORD are frameshift or splicing variants.…”

Section: Genetic Datamentioning

confidence: 99%

A novel mutation in SORD gene associated with distal hereditary motor neuropathies

Yuan,

Zhang,

Shang

et al. 2024

BMC Med Genomics

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Background Distal hereditary motor neuropathy (dHMN) is a heterogeneous group of hereditary diseases caused by the gradual degeneration of the lower motor neuron. More than 30 genes associated with dHMN have been reported, while 70–80% of those with the condition are still unable to receive a genetic diagnosis. Methods A 26-year-old man experiencing gradual weakness in his lower limbs was referred to our hospital, and data on clinical features, laboratory tests, and electrophysiological tests were collected. To identify the disease-causing mutation, we conducted whole exome sequencing (WES) and then validated it through Sanger sequencing for the proband and his parents. Silico analysis was performed to predict the pathogenesis of the identified mutations. A literature review of all reported mutations of the related gene for the disease was performed. Results The patient presented with dHMN phenotype harboring a novel homozygous variant c.361G > C (p.Ala121Pro) in SORD, inherited from his parents, respectively. A121 is a highly conserved site and the mutation was categorized as “likely pathogenic” according to the criteria and guidelines of the American College of Medical Genetics and Genomics (ACMG). A total of 13 published articles including 101 patients reported 18 SORD variants. Almost all described cases have the homozygous deletion variant c.757delG (p.A253Qfs*27) or compound heterozygous state of a combination of c.757delG (p.A253Qfs*27) with another variant. The variant c.361G > C (p.Ala121Pro) detected in our patient was the second homozygous variant in SORD-associated hereditary neuropathy. Conclusion One novel homozygous variant c.361G > C (p.Ala121Pro) in SORD was identified in a Chinese patient with dHMN phenotype, which expands the mutation spectrum of SORD-associated hereditary neuropathy and underscores the significance of screening for SORD variants in patients with undiagnosed hereditary neuropathy patients.

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“…Patients present a pure motor (dHMN) or sensory-motor (CMT2) neuropathy with motor symptoms more evident than sensory involvement [40 ▪▪ ]. In addition to the classical presentation, some patients show a nonlength-dependent neuropathy with prominent upper limb involvement and motor conduction slowing and block in electrophysiological studies [44].…”

Section: Novel Genesmentioning

confidence: 99%

Hereditary motor neuropathies

Frasquet

Sevilla

2022

Current Opinion in Neurology

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Purpose of reviewDistal hereditary motor neuropathies (dHMN) are a clinically and genetically diverse group of disorders that are characterized by length-dependent axonal degeneration of lower motor neurons. In this review, we will provide an overview of dHMN, and we will correlate the distinct clinical subtypes with their causative genes, focusing on the most recent advances in the field. Recent findingsDespite the massive use of new-generation sequencing (NGS) and the discovery of new genes, only a third of dHMN patients receive a molecular diagnosis. Thanks to international cooperation between researchers, new genes have been implicated in dHMN, such as SORD and VWA1. Mutations in SORD are the most frequent cause of autosomal recessive forms of dHMN. As a result of these findings, the potential benefits of some pharmacological compounds are being studied in cell and animal models, mainly targeting axonal transport and metabolic pathways. SummaryDespite the wide use of NGS, the diagnosis of dHMN remains a challenge. The low prevalence of dHMN makes international cooperation necessary in order to discover new genes and causal mechanisms. Genetic diagnosis of patients and identification of new pathomechanism are essential for the development of therapeutical clinical trials.

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Unusual upper limb features in SORD neuropathy

Cited by 6 publications

References 5 publications

A novel mutation in SORD gene associated with Distal Hereditary Motor Neuropathies

A novel mutation in SORD gene associated with Distal Hereditary Motor Neuropathies

A novel mutation in SORD gene associated with distal hereditary motor neuropathies

Hereditary motor neuropathies

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