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The genetic diagnoses are increasingly obtained with using the next generation sequencing (NGS). We applied the custom-design targeted NGS panel including 89 genes, together with genotyping and multiplex ligation-dependent probe amplification (MLPA) to identify a genetic spectrum of NMDs in 52 Polish patients. As a result, the genetic diagnosis was determined by NGS panel in 29 patients so its diagnostic utility is estimated at 55.8%. The most pathogenic variants were found in\n                    <jats:italic>CLCN1<\/jats:italic>\n                    , followed by\n                    <jats:italic>CAPN3<\/jats:italic>\n                    ,\n                    <jats:italic>SCN4A<\/jats:italic>\n                    , and\n                    <jats:italic>SGCA<\/jats:italic>\n                    genes. Genotyping of myotonic dystrophy type 1 and 2 (DM1 and DM2) as a secondary approach has been performed. The co-occurrence of\n                    <jats:italic>CAPN3<\/jats:italic>\n                    and\n                    <jats:italic>CNBP<\/jats:italic>\n                    mutations in one patient as well as\n                    <jats:italic>DYSF<\/jats:italic>\n                    and\n                    <jats:italic>CNBP<\/jats:italic>\n                    mutations in another suggests possibly more complex inheritance as well as expression of a phenotype. In 7 individuals with single nucleotide variant found in NGS testing, the MLPA of the\n                    <jats:italic>CAPN3<\/jats:italic>\n                    gene was performed detecting the deletion encompassing exons 2\u20148 in the\n                    <jats:italic>CAPN3<\/jats:italic>\n                    gene in one patient, confirming recessive limb-girdle muscular dystrophy type 1 (LGMDR1). Thirty patients obtained a genetic diagnosis (57.7%) after using NGS testing, genotyping and MLPA analysis. The study allowed for the identification of 27 known and 4 novel pathogenic\/likely pathogenic variants and variants of uncertain significance (VUS) associated with NMDs.\n                  <\/jats:p>\n                  <jats:p>In conclusion, the diagnostic approach with diverse molecular techniques enables to broaden the mutational spectrum and maximizes the diagnostic yield. Furthermore, the co-occurrence of DM2 and LGMD has been detected in 2 individuals.<\/jats:p>","DOI":"10.1007\/s10048-024-00762-y","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T01:01:41Z","timestamp":1715907701000},"page":"233-247","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Next generation sequencing panel as an effective approach to genetic testing in patients with a highly variable phenotype of neuromuscular disorders"],"prefix":"10.1007","volume":"25","author":[{"given":"Wiktoria","family":"Radziwonik-Fraczyk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewelina","family":"Elert-Dobkowska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marek","family":"Karpinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacek","family":"Pilch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"Ziora-Jakutowicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolanta","family":"Kubalska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominika","family":"Szczesniak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iwona","family":"Stepniak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacek","family":"Zaremba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Sulek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"762_CR1","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/s0720-048x(01)00399-0","volume":"40","author":"O Ozsarlak","year":"2001","unstructured":"Ozsarlak O, Schepens E, Parizel PM et al (2001) Hereditary neuromuscular diseases. 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Written informed consent was obtained from all participating patients or their guardians.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}