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.

• MeSH
• Adult MeSH
• Hereditary Sensory and Motor Neuropathy * diagnosis   epidemiology   genetics   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation MeSH
• Exome Sequencing MeSH
• Aged MeSH
• L-Iditol 2-Dehydrogenase genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• L-Iditol 2-Dehydrogenase MeSH

Hereditary motor and sensory neuropathy-type Lom (HMSNL), also known as CMT4D, a demyelinating neuropathy with late-onset deafness is an autosomal recessive disorder threatening Roma population worldwide. The clinical phenotype was reported in several case reports before the gene discovery. HMSNL is caused by a homozygous founder mutation p.Arg148* in the N-Myc downstream-regulated gene 1. Here, we report findings from the Czech Republic, where HMSNL was found in 12 Czech patients from eight families. In these 12 patients, 11 of the causes were due to p.Arg148* mutation inherited from both parents by the autosomal recessive mechanism. But in one case, the recessive mutation was inherited only from one parent (father) and unmasked owing to an uniparental isodisomy of the entire chromosome eight. The inherited peripheral neuropathy owing to an isodisomy of the whole chromosome pointed to an interesting, less frequent possibility of recessive disease and complications with genetic counseling.

• MeSH
• Charcot-Marie-Tooth Disease diagnosis   ethnology   genetics   physiopathology   MeSH
• Child MeSH
• Adult MeSH
• Founder Effect MeSH
• Gene Expression MeSH
• Phenotype MeSH
• Genetic Counseling MeSH
• Genotype MeSH
• Genes, Recessive MeSH
• Deafness physiopathology   MeSH
• Intracellular Signaling Peptides and Proteins genetics   MeSH
• Humans MeSH
• Chromosomes, Human, Pair 8 chemistry   MeSH
• Mutation * MeSH
• Child, Preschool MeSH
• Cell Cycle Proteins genetics   MeSH
• Refsum Disease diagnosis   ethnology   genetics   physiopathology   MeSH
• Roma * MeSH
• Uniparental Disomy * MeSH
• Age of Onset MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Intracellular Signaling Peptides and Proteins MeSH
• N-myc downstream-regulated gene 1 protein MeSH Browser
• Cell Cycle Proteins MeSH

BACKGROUND: Inherited peripheral neuropathies (IPN) are the most common inherited neurological condition. It represents a highly heterogeneous group, both clinically and genetically. Targeted disease specific gene panel massively parallel sequencing (MPS) seems to be a useful tool in diagnosis of disorders with high genetic heterogeneity. METHODS: In our study, we have designed, validated and updated our own custom gene panel of all known genes associated with IPN. One hundred and ninety-eight patients have been tested so far. Only patients in whom mutations in more common causes or relevant genes have already been excluded were enrolled. Five consecutive panel designs were prepared according to recent literature search, the last one covering ninety-three genes. Each patient was tested only once. All data were evaluated with at least two different pipelines. RESULTS: In summary, causative mutation has been found in fifty-one patients (26 %). The results were inconclusive in thirty-one (16 %) patients. No variants of likely significance to IPN were found in one hundred and sixteen (58 %) patients. CONCLUSION: MPS gene panel enables testing of all known IPN causes at once with high coverage and at an affordable cost making it truly a method of choice also in IPN. Gene panel testing results in several interesting results and findings.

• Keywords
• Charcot-Marie-Tooth, Inherited peripheral neuropathies, Mutation, Phenotype, Targeted gene panel testing,
• MeSH
• Charcot-Marie-Tooth Disease diagnosis   genetics   MeSH
• Cytoplasmic Dyneins genetics   MeSH
• DNA Helicases MeSH
• Genetic Testing methods   MeSH
• Genotype MeSH
• Hereditary Sensory and Motor Neuropathy genetics   MeSH
• Intracellular Signaling Peptides and Proteins genetics   MeSH
• Connexins genetics   MeSH
• Humans MeSH
• Multifunctional Enzymes MeSH
• Mutation MeSH
• Peripheral Nervous System Diseases diagnosis   genetics   MeSH
• Gap Junction beta-1 Protein MeSH
• Cell Cycle Proteins genetics   MeSH
• RNA Helicases genetics   MeSH
• Age of Onset MeSH
• High-Throughput Nucleotide Sequencing methods   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cytoplasmic Dyneins MeSH
• DNA Helicases MeSH
• DYNC1H1 protein, human MeSH Browser
• Intracellular Signaling Peptides and Proteins MeSH
• Connexins MeSH
• Multifunctional Enzymes MeSH
• N-myc downstream-regulated gene 1 protein MeSH Browser
• Cell Cycle Proteins MeSH
• RNA Helicases MeSH
• SETX protein, human MeSH Browser