{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T04:57:45Z","timestamp":1792299465094,"version":"4.4.0"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"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":["Clinical Genetics"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Disorders of intracellular trafficking are a group of inherited disorders, which often display multisystem phenotypes. Vacuolar protein sorting (VPS) subunit C, composed of VPS11, VPS18, VPS16, and VPS33A proteins, is involved in tethering of endosomes, lysosomes, and autophagosomes. Our group and others have previously described patients with a specific homozygous missense\n                    <jats:italic>VPS33A<\/jats:italic>\n                    variant, exhibiting a storage disease phenotype resembling mucopolysaccharidosis (MPS), termed \u201cMPS\u2010plus syndrome.\u201d Here, we report two siblings from a consanguineous Turkish\u2010Arabic family, who have overlapping features of MPS and intracellular trafficking disorders, including short stature, coarse facies, developmental delay, peripheral neuropathy, splenomegaly, spondylar dysplasia, congenital neutropenia, and high\u2010normal glycosaminoglycan excretion. Whole exome sequencing and familial segregation analyses led to the homozygous NM_022575.3:c.540G&gt;T; p.Trp180Cys variant in\n                    <jats:italic>VPS16<\/jats:italic>\n                    in both siblings. Multiple bioinformatic methods supported the pathogenicity of this variant. Different monoallelic null\n                    <jats:italic>VPS16<\/jats:italic>\n                    variants and a homozygous missense\n                    <jats:italic>VPS16<\/jats:italic>\n                    variant had been previously associated with dystonia. A biallelic intronic, probably splice\u2010altering variant in\n                    <jats:italic>VPS16<\/jats:italic>\n                    , causing an MPS\u2010plus syndrome\u2010like disease has been very recently reported in two individuals. The siblings presented herein display no dystonia, but have features of a multisystem storage disorder, representing a novel MPS\u2010plus syndrome\u2010like disease, associated for the first time with\n                    <jats:italic>VPS16<\/jats:italic>\n                    missense variants.\n                  <\/jats:p>","DOI":"10.1111\/cge.14002","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:38:55Z","timestamp":1621471135000},"page":"308-317","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Homozygous missense\n                    <scp>\n                      <i>VPS16<\/i>\n                    <\/scp>\n                    variant is associated with a novel disease, resembling mucopolysaccharidosis\u2010plus syndrome in two siblings"],"prefix":"10.1111","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9076-1388","authenticated-orcid":false,"given":"Y\u0131lmaz","family":"Y\u0131ld\u0131z","sequence":"first","affiliation":[{"name":"Division of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine Hacettepe University  Ankara Turkey"},{"name":"Department of Pediatric Metabolic Diseases Dr. Sami Ulus Training and Research Hospital for Maternity and Child Health  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-0510","authenticated-orcid":false,"given":"Can","family":"Ko\u015fukcu","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine Hacettepe University  Ankara Turkey"},{"name":"Department of Bioinformatics Institute of Health Sciences, Hacettepe University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6672-8393","authenticated-orcid":false,"given":"Damla","family":"Ayg\u00fcn","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine Hacettepe University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0862-3961","authenticated-orcid":false,"given":"Meltem","family":"Ak\u00e7aboy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Dr. Sami Ulus Training and Research Hospital for Maternity and Child Health  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2203-5904","authenticated-orcid":false,"given":"Fatma Zehra","family":"\u00d6ztek \u00c7elebi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Dr. Sami Ulus Training and Research Hospital for Maternity and Child Health  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4639-2081","authenticated-orcid":false,"given":"Yasemin","family":"Ta\u015fc\u0131 Y\u0131ld\u0131z","sequence":"additional","affiliation":[{"name":"Department of Pediatric Radiology Dr. Sami Ulus Training and Research Hospital for Maternity and Child Health  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6146-3509","authenticated-orcid":false,"given":"G\u00fclseren","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Dr. Sami Ulus Training and Research Hospital for Maternity and Child Health  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2921-5270","authenticated-orcid":false,"given":"Caner","family":"Aytekin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Allergy and Immunology Dr. Sami Ulus Training and Research Hospital for Maternity and Child Health  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-023X","authenticated-orcid":false,"given":"Deniz","family":"Y\u00fcksel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Dr. Sami Ulus Training and Research Hospital for Maternity and Child Health  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1466-5746","authenticated-orcid":false,"given":"\u0130ncilay","family":"Lay","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine Hacettepe University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0283-635X","authenticated-orcid":false,"given":"R\u0131za K\u00f6ksal","family":"\u00d6zg\u00fcl","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine Hacettepe University  Ankara Turkey"},{"name":"Institute of Child Health, Hacettepe University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1104-9902","authenticated-orcid":false,"given":"Ali","family":"Dursun","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine Hacettepe University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.189134"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0000000000000149"},{"key":"e_1_2_8_4_1","first-page":"173","article-title":"Mutation in VPS33A affects metabolism of glycosaminoglycans: a new type of mucopolysaccharidosis with severe systemic symptoms","volume":"26","author":"Kondo H","year":"2017","journal-title":"Hum Mol 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