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. 2021 Apr 19;11(1):8443.
doi: 10.1038/s41598-021-86857-0.

Biallelic variants in the SORD gene are one of the most common causes of hereditary neuropathy among Czech patients

P Laššuthová  1 , R Mazanec  2 , D Staněk  3 , L Sedláčková  3 , B Plevová  3   4 , J Haberlová  4 , P Seeman  3
Affiliations

Biallelic variants in the SORD gene are one of the most common causes of hereditary neuropathy among Czech patients

P Laššuthová et al. Sci Rep. .

Abstract

Recently, biallelic variants in the SORD gene were identified as causal for axonal hereditary neuropathy (HN). We ascertained the spectrum and frequency of SORD variants among a large cohort of Czech patients with unknown cause of HN. Exome sequencing data were analysed for SORD (58 patients). The prevalent c.757del variant was tested with fragment analysis (931 patients). Sanger sequencing in additional 70 patients was done. PCR primers were designed to amplify the SORD gene with the exclusion of the pseudogene SORD2P. Sequence differences between gene and pseudogene were identified and frequencies of SNPs were calculated. Eighteen patients from 16 unrelated families with biallelic variants in the SORD gene were found and the c.757del was present in all patients on at least one allele. Three novel, probably pathogenic, variants were detected, always in a heterozygous state in combination with the c.757del on the second allele. Patients presented with a slowly progressive axonal HN. Almost all patients had moderate pes cavus deformity. SORD neuropathy is frequent in Czech patients and the third most common cause of autosomal recessive HN. The c.757del is highly prevalent. Specific amplification of the SORD gene with the exclusion of the pseudogene is essential for a precise molecular diagnostics.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Workflow of the study. Four different analyses were done. In total, biallelic SORD variants were identified in 18 patients from 16 unrelated families. Prevalent variant is the c.757del.
Figure 2
Figure 2
The sequence differences of SORD and SORD2P. Blast search for SORD and SORD2P with alignment view pairwise with dots for identities (https://blast.ncbi.nlm.nih.gov). Several features are highlighted: red squares = differences; green rectangles = PCR primers; orange rectangles = sequencing primer; blue arrow = start and end of the exon; 1st primer = primer from original study; 2nd primer = our primer; grey rectangles with % = population frequency of that SNP in gnomAD for SORD.
Figure 3
Figure 3
Variants in the SORD gene detected in this study. Upper part - The structure of the SORD gene with nine coding exons. Middle part - Sanger sequences of variants detected in the study; detected novel variants are in pink. HET - hetrozygous; HOM-hoomzygous. Lower part - The conservation of amino acids based on a multiple sequence alignment analysis for missense variants detected in the study (https://www.ebi.ac.uk/Tools/msa/).
Figure 4
Figure 4
The pedigrees of selected families. HOM homozygous, w wild type; Pedigrees for families where at least two family members were tested are shown.
Figure 5
Figure 5
The SORD gene structure and published variants. Above the gene: variants found in this study. Below the gene are previously published variants. Red flags describe novel variants found in this study.
See this image and copyright information in PMC

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