{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:49Z","timestamp":1787014009104,"version":"build-2736575974"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD093570 01 A1 (PI)"],"award-info":[{"award-number":["R01 HD093570 01 A1 (PI)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    RNA exosome is a highly conserved ribonuclease complex essential for RNA processing and degradation. Bi\u2010allelic variants in exosome subunits\n                    <jats:italic>EXOSC3, EXOSC8<\/jats:italic>\n                    and\n                    <jats:italic>EXOSC9<\/jats:italic>\n                    have been reported to cause pontocerebellar hypoplasia type 1B, type 1C and type 1D, respectively, while those in\n                    <jats:italic>EXOSC2<\/jats:italic>\n                    cause short stature, hearing loss, retinitis pigmentosa and distinctive facies. We ascertained an 8\u2010months\u2010old male with developmental delay, microcephaly, subtle dysmorphism and hypotonia. Pontocerebellar hypoplasia and delayed myelination were noted on neuroimaging. A similarly affected elder sibling succumbed at the age of 4\u2010years 6\u2010months. Chromosomal microarray returned normal results. Exome sequencing revealed a homozygous missense variant, c.104C\u2009&gt;\u2009T p.(Ser35Leu) in\n                    <jats:italic>EXOSC1<\/jats:italic>\n                    (NM_016046.5) as the possible candidate.\n                    <jats:italic>In silico<\/jats:italic>\n                    mutagenesis revealed loss of a polar contact with neighboring Leu37 residue. Quantitative real\u2010time PCR indicated no appreciable differences in\n                    <jats:italic>EXOSC1<\/jats:italic>\n                    transcript levels. Immunoblotting and blue native PAGE revealed reduction in the EXOSC1 protein levels and EXO9 complex in the proband, respectively. We herein report an individual with the bi\u2010allelic variant c.104C&gt;T p.(Ser35Leu) in\n                    <jats:italic>EXOSC1<\/jats:italic>\n                    and clinical features of pontocerebellar hypoplasia type 1. Immunoblotting and blue native PAGE provide evidence for the pathogenicity of the variant. Thus, we propose\n                    <jats:italic>EXOSC1<\/jats:italic>\n                    as a novel candidate gene for pontocerebellar hypoplasia.\n                  <\/jats:p>","DOI":"10.1111\/cge.13928","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T06:51:15Z","timestamp":1611039075000},"page":"594-600","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Bi\u2010allelic missense variant, p.\n                    <scp>Ser35Leu<\/scp>\n                    in\n                    <scp>\n                      <i>EXOSC1<\/i>\n                    <\/scp>\n                    is associated with pontocerebellar hypoplasia"],"prefix":"10.1111","volume":"99","author":[{"given":"Puneeth H.","family":"Somashekar","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College, Manipal Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parneet","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College, Manipal Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshi","family":"Stephen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College, Manipal Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal Singh","family":"Guleria","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College, Manipal Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajagopal","family":"Kadavigere","sequence":"additional","affiliation":[{"name":"Department of Radiodiagnosis and Imaging, Kasturba Medical College, Manipal Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-8239","authenticated-orcid":false,"given":"Katta Mohan","family":"Girisha","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College, Manipal Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Bielas","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Upadhyai","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College, Manipal Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2471-4094","authenticated-orcid":false,"given":"Anju","family":"Shukla","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College, Manipal Manipal Academy of Higher Education  Manipal 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