Association of SORD mutation with autosomal recessive asymmetric distal hereditary motor neuropathy

Alluqmani, Majed; Basit, Sulman

doi:10.1186/s12920-022-01238-4

Cited by 5 publications

(4 citation statements)

References 21 publications

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“…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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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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“…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%

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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“…1 To date, an additional 22 pathogenic variants in SORD have been reported, of which 19 are either homozygous or compound heterozygous with p.Ala253GlnfsTer27. [1][2][3][4][5][6][7] The SORD protein is a zinc-dependent homotetramer composed of 38-kDa subunits with catalytic domains that include a zinc-binding domain and tetramer interface 8,9 It is the rate-limiting enzyme in the polyol pathway of glucose metabolism; loss of enzyme function and consequent sorbitol accumulation may lead to synaptic degeneration and progressive dyskinesia. 1 Biallelic SORD variants are responsible for clinically distinct entities which we collectively refer to as SORD-related PN (SORD-PN), including Charcot-Marie-Tooth type 2 (CMT2) and distal hereditary motor neuropathy (dHMN).…”

Section: Introductionmentioning

confidence: 99%

“…The dominant pathogenic variant in SORD , c.757delG; p.Ala253GlnfsTer27, is the gene most frequently associated with recessive axonal neuropathy, with a carrier frequency of ~3/1000 individuals 1 . To date, an additional 22 pathogenic variants in SORD have been reported, of which 19 are either homozygous or compound heterozygous with p.Ala253GlnfsTer27 1–7 . The SORD protein is a zinc‐dependent homotetramer composed of 38‐kDa subunits with catalytic domains that include a zinc‐binding domain and tetramer interface 8,9 It is the rate‐limiting enzyme in the polyol pathway of glucose metabolism; loss of enzyme function and consequent sorbitol accumulation may lead to synaptic degeneration and progressive dyskinesia 1 …”

Section: Introductionmentioning

confidence: 99%

Expanding the genetic and clinical spectrum of SORD‐related peripheral neuropathy by reporting a novel variant c.210T>G and evidence of subclinical muscle involvement

Xie

Zeng

et al. 2023

J Peripheral Nervous Sys

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Background and AimsBiallelic variants in the sorbitol dehydrogenase (SORD) gene have been identified as the genetic cause of autosomal recessive (AR) peripheral neuropathy (PN) manifesting as Charcot‐Marie‐Tooth disease type 2 (CMT2) or distal hereditary motor neuropathy (dHMN). We aim to observe the genetic and clinical spectrum of a cohort of patients with SORD‐related PN (SORD‐PN).MethodsA total of 107 patients with AR or sporadic CMT2/dHMN underwent molecular diagnosis by whole‐exome sequencing and subsequent Sanger sequencing validation. Available phenotypic data for SORD‐PN were collected and analyzed.ResultsEleven (10.28%) of 107 patients were identified as SORD‐PN, including 4 with CMT2 and 7 with dHMN. The SORD variant c.210T>G;p.His70Gln in F‐d3 was firstly reported and subsequent analysis showed that it resulted in loss of SORD enzyme function. Evidence of subclinical muscle involvement was frequently detected in patients with SORD‐PN, including mildly to moderately elevated serum creatine kinase (CK) levels in 10 patients, myogenic electrophysiological changes in 1 patient, and muscle edema in 5 patients undergoing lower extremity MRI. Fasting serum sorbitol level was 88‐fold higher in SORD‐PN patients (9.69±1.07mg/l) than in healthy heterozygous subjects (0.11±0.01mg/l) and 138‐fold higher than in healthy controls (0.07±0.02mg/l).InterpretationThe novel SORD variant c.210T>G;p.His70Gln and evidence of subclinical muscle involvement were identified, which expanded the genetic and clinical spectrum of SORD‐PN. Subclinical muscle involvement might be a common but easily overlooked clinical feature. The serum CK and fasting serum sorbitol levels were expected to be sensitive biomarkers confirmed by follow‐up cohort study.This article is protected by copyright. All rights reserved.

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Association of SORD mutation with autosomal recessive asymmetric distal hereditary motor neuropathy

Cited by 5 publications

References 21 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

Expanding the genetic and clinical spectrum of SORD‐related peripheral neuropathy by reporting a novel variant c.210T>G and evidence of subclinical muscle involvement

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