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Genetic analysis of the\n                    <jats:italic>ARSA<\/jats:italic>\n                    gene is important in MLD diagnosis and screening of family members. In addition, more information on genotype prevalence will help interpreting MLD population differences between countries. In this study, we identified 31 different\n                    <jats:italic>ARSA<\/jats:italic>\n                    variants in the patient cohort (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200967) of the Dutch expertise center for MLD. The most frequently found variant, c.1283C &gt; T, p.(Pro428Leu), was present in 43 (64%) patients and resulted in a high prevalence of the juvenile MLD type (58%) in The Netherlands. Furthermore, we observed in five out of six patients with a non-Caucasian ethnic background previously unreported pathogenic\n                    <jats:italic>ARSA<\/jats:italic>\n                    variants. In total, we report ten novel variants including four missense, two nonsense, and two frameshift variants and one in-frame indel, which were all predicted to be disease causing in silico. In addition, one silent variant was found, c.1200C &gt; T, that most likely resulted in erroneous exonic splicing, including partial skipping of exon 7. The c.1200C &gt; T variant was inherited in cis with the pseudodeficiency allele c.1055A &gt; G, p.(Asn352Ser) + \u221796A &gt; G. With this study we provide a genetic base of the unique MLD phenotype distribution in The Netherlands. In addition, our study demonstrated the importance of genetic analysis in MLD diagnosis and the increased likelihood of unreported, pathogenic\n                    <jats:italic>ARSA<\/jats:italic>\n                    variants in patients with non-Caucasian ethnic backgrounds.\n                  <\/jats:p>","DOI":"10.1007\/s10048-020-00621-6","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T21:03:41Z","timestamp":1594069421000},"page":"289-299","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Metachromatic leukodystrophy genotypes in The Netherlands reveal novel pathogenic ARSA variants in non-Caucasian patients"],"prefix":"10.1007","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2945-6784","authenticated-orcid":false,"given":"Shanice","family":"Beerepoot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvy J.M.","family":"van Dooren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2509-3648","authenticated-orcid":false,"given":"Gajja S.","family":"Salomons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2232-6952","authenticated-orcid":false,"given":"Jaap Jan","family":"Boelens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin H.","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8912-0954","authenticated-orcid":false,"given":"Marjo S.","family":"van der Knaap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7989-4910","authenticated-orcid":false,"given":"Andr\u00e9 B.P.","family":"van Kuilenburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1721-0728","authenticated-orcid":false,"given":"Nicole I.","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,7]]},"reference":[{"key":"621_CR1","unstructured":"Von Figura K, Gieselmann V, Jaeken J (2001) Metachromatic leukodystrophy. 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