Long read sequencing overcomes challenges in the diagnosis of <scp><i>SORD</i></scp> neuropathy

Grosz, Bianca R; Stevanovski, Igor; Negri, Sara; Ellis, Melina; Barnes, Stephanie L.; Reddel, Stephen W.; Vucic, Steve; Nicholson, Garth A.; Cortese, Andrea; Kumar, Kishore R.; Kennerson, Marina

doi:10.1111/jns.12485

Cited by 12 publications

(4 citation statements)

References 25 publications

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“…We found different sorbitol normal values in the literature. Grosz et al [19] measured the plasma sorbitol level of one control patient, which was 0.2 mg/L, consistent with the 0.164 ± 0.044 mg/L published by Preston and Calle [20] (13 healthy control patients) and the 0.2 ± 0.068 mg/L reported by Shetty et al [21] (12 patients measured).…”

Section: Discussionsupporting

confidence: 81%

SORD‐related peripheral neuropathy in a French and Swiss cohort: Clinical features, genetic analyses, and sorbitol dosages

Nicolas

Fernández‐Eulate

Pégat

et al. 2023

Euro J of Neurology

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Background and purposeBiallelic variants in SORD have been reported as one of the main recessive causes for hereditary peripheral neuropathies such as Charcot–Marie–Tooth disease type 2 (CMT2) and distal hereditary motor neuropathy (dHMN) resulting in lower limb (LL) weakness and muscular atrophy. In this study, phenotype and genotype landscapes of SORD‐related peripheral neuropathies were described in a French and Swiss cohort. Serum sorbitol dosages were used to classify SORD variants.MethodsPatients followed at neuromuscular reference centres in France and Switzerland were ascertained. Sanger sequencing and next generation sequencing were performed to sequence SORD, and mass spectrometry was used to measure patients' serum sorbitol.ResultsThirty patients had SORD peripheral neuropathy associating LL weakness with muscular atrophy, foot deformities (87%), and sometimes proximal LL weakness (20%) or distal upper limb weakness (50%). Eighteen had dHMN, nine had CMT2, and three had intermediate CMT. Most of them had a mild or moderate disease severity. Sixteen carried a homozygous c.757delG (p.Ala253Glnfs*27) variant, and 11 carried compound heterozygous variants, among which four variants were not yet reported: c.403C > G, c.379G > A, c.68_100 + 1dup, and c.850dup. Two unrelated patients with different origins carried a homozygous c.458C > A variant, and one patient carried a new homozygous c.786 + 5G > A variant. Mean serum sorbitol levels were 17.01 mg/L ± 8.9 SD for patients carrying SORD variants.ConclusionsThis SORD‐inherited peripheral neuropathy cohort of 30 patients showed homogeneous clinical presentation and systematically elevated sorbitol levels (22‐fold) compared to controls, with both diagnostic and potential therapeutic implications.

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Section: Discussionsupporting

confidence: 81%

SORD‐related peripheral neuropathy in a French and Swiss cohort: Clinical features, genetic analyses, and sorbitol dosages

Nicolas

Fernández‐Eulate

Pégat

et al. 2023

Euro J of Neurology

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“…42 For instance, long-read sequencing can detect single nucleotide variants and indels, now approaching the accuracy of short-read sequencing. 43 But long-reads can also differentiate between homologous pseudogenes like SORD/SORDP2 and GBA/GBAP1 44,45 and phasing variants for haplotype reconstruction 46 to aid in the reclassification of variants of uncertain significance 47 and are essential for the design of targeted gene editing. 48 Highly repetitive sequences are also well resolved by long-reads, [49][50][51] with recent advances reported for resolving tandem repeats at a genome scale using PacBio HiFi sequencing, which was accompanied by a database of nearly 1 million tandem repeats and associated methylation profiles.…”

Section: Advances In Long-read Sequencingmentioning

confidence: 99%

The Next, Next-Generation of Sequencing, Promising to Boost Research and Clinical Practice

Kumar,

Cowley,

Davis

2024

Semin Thromb Hemost

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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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Long read sequencing overcomes challenges in the diagnosis of SORD neuropathy

Cited by 12 publications

References 25 publications

SORD‐related peripheral neuropathy in a French and Swiss cohort: Clinical features, genetic analyses, and sorbitol dosages

SORD‐related peripheral neuropathy in a French and Swiss cohort: Clinical features, genetic analyses, and sorbitol dosages

The Next, Next-Generation of Sequencing, Promising to Boost Research and Clinical Practice

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

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