{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:24:39Z","timestamp":1775150679636,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Case Reports in Genetics"],"published-print":{"date-parts":[[2020,9,24]]},"abstract":"<jats:p>Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations of the <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mi>V<\/mml:mi><mml:mi>P<\/mml:mi><mml:mi>S<\/mml:mi><mml:mn>33<\/mml:mn><mml:mi>B<\/mml:mi><\/mml:math> encoding the vacuolar protein sorting 33B (VPS33B), which is involved in the intracellular protein sorting and vesicular trafficking. We report a rare case of ARC syndrome without arthrogryposis caused by a novel mutation of <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mi>V<\/mml:mi><mml:mi>P<\/mml:mi><mml:mi>S<\/mml:mi><mml:mn>33<\/mml:mn><mml:mi>B<\/mml:mi><\/mml:math>. A female patient of Greek origin presented on the 14<jats:sup>th<\/jats:sup> day of life with renal tubular acidosis, Fanconi syndrome, nephrogenic diabetes insipidus, and cholestasis with normal gamma-glutamyl transpeptidase, without arthrogryposis and dysmorphic features. She was born to apparently healthy, nonconsanguineous parents. Additional features included dry and scaling skin, generalized hypotonia, hypoplastic corpus callosum, neurodevelopmental delay, failure to thrive, short stature, recurrent febrile episodes with and without infections, and gastrointestinal bleeding. DNA testing revealed that the patient was homozygous for the novel c.1098_1099delTG (p.Glu367Alafs<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mi>\u2217<\/mml:mi><\/mml:math>17) mutation of exon 14 of <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\"><mml:mi>V<\/mml:mi><mml:mi>P<\/mml:mi><mml:mi>S<\/mml:mi><mml:mn>33<\/mml:mn><mml:mi>B<\/mml:mi><\/mml:math> gene (NM_018668) on chromosome 15q26.1, leading to a nonsense frameshift variant of VPS33B with premature termination of translation. Her parents were heterozygous for the same <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\"><mml:mi>V<\/mml:mi><mml:mi>P<\/mml:mi><mml:mi>S<\/mml:mi><mml:mn>33<\/mml:mn><mml:mi>B<\/mml:mi><\/mml:math> mutation. The prognosis was predictably poor in the context of the intractable polyuria necessitating long-term parenteral fluid administration via indwelling central catheter leading to catheter-related sepsis, to which she eventually succumbed at the age of 7 months. This is the first published <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\"><mml:mi>V<\/mml:mi><mml:mi>P<\/mml:mi><mml:mi>S<\/mml:mi><mml:mn>33<\/mml:mn><mml:mi>B<\/mml:mi><\/mml:math> mutation in an ARC patient of Greek origin. The current case adds to the spectrum of ARC-associated <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M8\"><mml:mi>V<\/mml:mi><mml:mi>P<\/mml:mi><mml:mi>S<\/mml:mi><mml:mn>33<\/mml:mn><mml:mi>B<\/mml:mi><\/mml:math> mutations and provides evidence supporting the existence of incomplete ARC phenotype. Increased awareness and early genetic testing for ARC are suggested in cases with isolated cholestasis and\/or renal tubular dysfunction, even in the absence of arthrogryposis.<\/jats:p>","DOI":"10.1155\/2020\/8872294","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T23:34:01Z","timestamp":1600990441000},"page":"1-8","source":"Crossref","is-referenced-by-count":6,"title":["A Novel Mutation of <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>V<\/mml:mi><mml:mi>P<\/mml:mi><mml:mi>S<\/mml:mi><mml:mn>33<\/mml:mn><mml:mi>B<\/mml:mi><\/mml:math> Gene Associated with Incomplete Arthrogryposis-Renal Dysfunction-Cholestasis Phenotype"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7361-0510","authenticated-orcid":true,"given":"Eleni","family":"Agakidou","sequence":"first","affiliation":[{"name":"1st Department of Neonatology, Aristotle University of Thessaloniki, Ippokration General Hospital, Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charalampos","family":"Agakidis","sequence":"additional","affiliation":[{"name":"1st Department of Pediatrics, Aristotle University of Thessaloniki, Ippokration General Hospital, Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marios","family":"Kambouris","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Pathology and Laboratory Medicine, Sidra Medicine Hospital, Doha, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoleta","family":"Printza","sequence":"additional","affiliation":[{"name":"1st Department of Pediatrics, Aristotle University of Thessaloniki, Ippokration General Hospital, Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Farini","sequence":"additional","affiliation":[{"name":"1st Department of Neonatology, Aristotle University of Thessaloniki, Ippokration General Hospital, Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elina","family":"Vourda","sequence":"additional","affiliation":[{"name":"1st Department of Pediatrics, Aristotle University of Thessaloniki, Ippokration General Hospital, Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Spyridon","family":"Gerou","sequence":"additional","affiliation":[{"name":"Analysis Medical S.A. 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