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MPS is most frequently inherited in an autosomal recessive fashion but X\u2010linked and autosomal dominant forms also occur. Advances in genomic technologies have identified many genetic causes of MPS\u2010related disorders and genetic diagnosis requires large targeted next generation sequencing gene panels or genome\u2010wide sequencing approaches. Using the Illumina TruSightOne clinical exome assay, we identified a recurrent heterozygous missense substitution in <jats:italic>TPM2<\/jats:italic> (encoding beta tropomyosin) in three unrelated individuals. This was confirmed to have arisen as a de novo event in the two patients with parental samples. <jats:italic>TPM2<\/jats:italic> mutations have previously been described in association with a variety of dominantly inherited neuromuscular phenotypes including nemaline myopathy, congenital fibre\u2010type disproportion, distal arthrogryposis and trismus pseudocamptodactyly, and in a patient with autosomal recessive Escobar syndrome and a nemaline myopathy. The three cases reported here had overlapping but variable features. Our findings expand the range of <jats:italic>TMP2<\/jats:italic>\u2010related phenotypes and indicate that de novo <jats:italic>TMP2<\/jats:italic> mutations should be considered in isolated cases of MPS\u2010related conditions.<\/jats:p>","DOI":"10.1111\/cge.13728","type":"journal-article","created":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T21:04:22Z","timestamp":1582578262000},"page":"908-914","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A recurrent pathogenic variant in <scp><i>TPM2<\/i><\/scp> reveals further phenotypic and genetic heterogeneity in multiple pterygium syndrome\u2010related disorders"],"prefix":"10.1111","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7459-0176","authenticated-orcid":false,"given":"Julie","family":"Vogt","sequence":"first","affiliation":[{"name":"West Midlands Regional Genetics Service Birmingham Women's and Children's Hospital  Birmingham 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