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
• Charcotova-Marieova-Toothova nemoc diagnóza   etnologie   genetika   patofyziologie   MeSH
• dítě MeSH
• dospělí MeSH
• efekt zakladatele MeSH
• exprese genu MeSH
• fenotyp MeSH
• genetické poradenství MeSH
• genotyp MeSH
• geny recesivní MeSH
• hluchota patofyziologie   MeSH
• intracelulární signální peptidy a proteiny genetika   MeSH
• lidé MeSH
• lidské chromozomy, pár 8 chemie   MeSH
• mutace * MeSH
• předškolní dítě MeSH
• proteiny buněčného cyklu genetika   MeSH
• Refsumova nemoc diagnóza   etnologie   genetika   patofyziologie   MeSH
• Romové * MeSH
• uniparentální disomie * MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• intracelulární signální peptidy a proteiny MeSH
• N-myc downstream-regulated gene 1 protein MeSH Prohlížeč
• proteiny buněčného cyklu 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.

• Klíčová slova
• Charcot-Marie-Tooth, Inherited peripheral neuropathies, Mutation, Phenotype, Targeted gene panel testing,
• MeSH
• Charcotova-Marieova-Toothova nemoc diagnóza   genetika   MeSH
• cytoplazmatické dyneiny genetika   MeSH
• DNA-helikasy MeSH
• genetické testování metody   MeSH
• genotyp MeSH
• hereditární motorické a senzitivní neuropatie genetika   MeSH
• intracelulární signální peptidy a proteiny genetika   MeSH
• konexiny genetika   MeSH
• lidé MeSH
• multifunkční enzymy MeSH
• mutace MeSH
• nemoci periferního nervového systému diagnóza   genetika   MeSH
• protein beta 1 mezerového spoje MeSH
• proteiny buněčného cyklu genetika   MeSH
• RNA-helikasy genetika   MeSH
• věk při počátku nemoci MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytoplazmatické dyneiny MeSH
• DNA-helikasy MeSH
• DYNC1H1 protein, human MeSH Prohlížeč
• intracelulární signální peptidy a proteiny MeSH
• konexiny MeSH
• multifunkční enzymy MeSH
• N-myc downstream-regulated gene 1 protein MeSH Prohlížeč
• proteiny buněčného cyklu MeSH
• RNA-helikasy MeSH
• SETX protein, human MeSH Prohlížeč