{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:27:30Z","timestamp":1786976850363,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"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":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Verheij syndrome (VRJS) is a rare craniofacial spliceosomopathy presenting with craniofacial dysmorphism, multiple congenital anomalies and variable neurodevelopmental delay. It is caused by single nucleotide variants (SNVs) in\n                    <jats:italic>PUF60<\/jats:italic>\n                    or interstitial deletions of the 8q24.3 region.\n                    <jats:italic>PUF60<\/jats:italic>\n                    encodes a splicing factor which forms part of the spliceosome. To date, 36 patients with a sole diagnosis of VRJS due to disease\u2010causing\n                    <jats:italic>PUF60<\/jats:italic>\n                    SNVs have been reported in peer\u2010reviewed publications. Although the depth of their phenotyping has varied greatly, they exhibit marked phenotypic heterogeneity. We report 10 additional unrelated patients, including the first described patients of Khmer, Indian, and Vietnamese ethnicities, and the eldest patient to date, with 10 heterozygous\n                    <jats:italic>PUF60<\/jats:italic>\n                    variants identified through exome sequencing, 8 previously unreported. All patients underwent deep phenotyping identifying variable dysmorphism, growth delay, neurodevelopmental delay, and multiple congenital anomalies, including several unique features. The eldest patient is the only reported individual with a germline variant and neither neurodevelopmental delay nor intellectual disability. In combining these detailed phenotypic data with that of previously reported patients (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u200946), we further refine the known frequencies of features associated with VRJS. These include neurodevelopmental delay\/intellectual disability (98%), axial skeletal anomalies (74%), appendicular skeletal anomalies (73%), oral anomalies (68%), short stature (66%), cardiac anomalies (63%), brain malformations (48%), hearing loss (46%), microcephaly (41%), colobomata (38%), and other ocular anomalies (65%). This case series, incorporating three patients from previously unreported ethnic backgrounds, further delineates the broad pleiotropy and mutational spectrum of\n                    <jats:italic>PUF60<\/jats:italic>\n                    pathogenic variants.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62950","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T06:09:18Z","timestamp":1660716558000},"page":"3432-3447","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The diverse pleiotropic effects of spliceosomal protein\n                    <scp>PUF60<\/scp>\n                    : A case series of Verheij syndrome"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6744-1810","authenticated-orcid":false,"given":"Andrew Paul","family":"Fennell","sequence":"first","affiliation":[{"name":"Monash Genetics Monash Health  Melbourne 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