{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T19:41:28Z","timestamp":1786822888685,"version":"build-2736575974"},"reference-count":11,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Biallelic pathogenic variants in phosphopantothenoylcysteine synthetase, <jats:italic>PPCS<\/jats:italic>, are a rare cause of a severe early\u2010onset dilated cardiomyopathy with high morbidity and mortality. To date, only five individuals with <jats:italic>PPCS<\/jats:italic>\u2010mutations have been reported. Here, we report a female infant who presented in the neonatal period with hypotonia, a necrotizing myopathy with intermittent rhabdomyolysis and other extracardiac manifestations before developing a progressive and ultimately fatal dilated cardiomyopathy. Gene agnostic trio genome sequencing revealed two rare variants in the <jats:italic>PPCS<\/jats:italic> [MIM: 609853] <jats:italic>in trans<\/jats:italic>, a previously reported pathogenic c.320_334del p. (Pro107_Ala111del) variant, and a c.613\u20103C&gt;G intronic variant of uncertain significance. Functional studies confirmed the likely pathogenicity of this variant. Our case provides clinical and histopathological evidence for an associated neuromuscular phenotype not previously recognized and expands the evolving phenotypic spectrum of <jats:italic>PPCS<\/jats:italic>\u2010related disorders. We also performed a literature search of all previously published cases and summarize the common features.<\/jats:p>","DOI":"10.1002\/ajmg.a.62848","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T13:07:27Z","timestamp":1653570447000},"page":"2783-2789","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Novel phosphopantothenoylcysteine synthetase (<scp><i>PPCS<\/i><\/scp>) mutations with prominent neuromuscular features: Expanding the phenotypical spectrum of <scp><i>PPCS<\/i><\/scp>\u2010related disorders"],"prefix":"10.1002","volume":"188","author":[{"given":"Aishin","family":"Lok","sequence":"first","affiliation":[{"name":"Neonatal Unit, Evelina London Children's Hospital Guy's &amp; St Thomas' Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Fernandez\u2010Garcia","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, Neuromuscular Service, Evelina London Children's Hospital Guy's &amp; St Thomas' Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences University of Newcastle  Newcastle Upon Tyne UK"},{"name":"NHS Highly Specialised for Rare Mitochondrial Disorders of Adults and Children Newcastle Upon Tyne Hospitals NHS Foundation Trust  Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"French","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"MacFarland","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences University of Newcastle  Newcastle Upon Tyne UK"},{"name":"NHS Highly Specialised for Rare Mitochondrial Disorders of Adults and Children Newcastle Upon Tyne Hospitals NHS Foundation Trust  Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istvan","family":"Bodi","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuropathology King's College Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Champion","sequence":"additional","affiliation":[{"name":"Department of Children's Inherited Metabolic Diseases, Evelina London Children's Hospital Guy's &amp; St Thomas' Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7634-9207","authenticated-orcid":false,"given":"Dragana","family":"Josifova","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Guy's Hospital Guy's &amp; St Thomas' Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances Lucy","family":"Raymond","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arcangela","family":"Iuso","sequence":"additional","affiliation":[{"name":"Institute of Neurogenomics, Helmholtz Zentrum Munchen  Munich Germany"},{"name":"Institute of Human Genetics Technical University of Munich, School of Medicine  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7159-3427","authenticated-orcid":false,"given":"Heinz","family":"Jungbluth","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, Neuromuscular Service, Evelina London Children's Hospital Guy's &amp; St Thomas' Hospital NHS Foundation Trust  London UK"},{"name":"Randall Centre for Cell and Molecular Biophysics, Muscle Signalling Section Faculty of Life Sciences and Medicine (FoLSM)  London UK"},{"name":"Department of Paediatric Neurology, Evelina London Children's Hospital Guy's &amp; St Thomas' Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3397-6563","authenticated-orcid":false,"given":"Anna","family":"Milan","sequence":"additional","affiliation":[{"name":"Neonatal Unit, Evelina London Children's Hospital Guy's &amp; St Thomas' Hospital NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul R.","family":"Singh","sequence":"additional","affiliation":[{"name":"Neonatal Unit, Evelina London Children's Hospital Guy's &amp; St Thomas' Hospital NHS Foundation Trust  London UK"},{"name":"Department of Paediatric Neurology, Evelina London Children's Hospital Guy's &amp; 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