{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T10:01:18Z","timestamp":1780308078980,"version":"3.54.0"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The embryonic development of the cerebellum is orchestrated through a dynamic process that governs the interplay of Purkinje and granule cell populations. SKOR2 (Fussel 18) is a transcriptional co\u2010repressor that increases SHH (sonic hedgehog) expression which is a potent signal for granule cell proliferation and integration into the complex neuronal network that underlies cerebellar function and development. Complete loss of Skor2 function in a murine model has been shown to result in cerebellar hypoplasia due to severe disruption of the cerebellar vermis. Through GeneMatcher we identified eight individuals from five unrelated families with compound heterozygous or homozygous loss of function, splice site and missense variants in\n                    <jats:italic>SKOR2<\/jats:italic>\n                    associated with a phenotypic spectrum of cerebellar hypoplasia, microcephaly, ataxia, developmental delays and intellectual disability. Variants identified in\n                    <jats:italic>SKOR2<\/jats:italic>\n                    included homozygous c.1877delC; p.Pro626Glnfsx156 in the first individual, homozygous c.2752\u2009+\u20091G&gt;T in the second and third individuals, compound heterozygous c.757T&gt;G p.C253G, c.949T&gt;A p.S317T in the fourth individual, homozygous c.421_424del (p.Asp141Ilefs*118) in the fifth, sixth, and seventh individuals, and a homozygous c.1169C&gt;A; p.Ser390* in the eighth individual. The eight individuals had various degrees of developmental and speech delays, as well as cerebellar hypoplasia identified in some of them. In silico analysis supported pathogenicity of most of\n                    <jats:italic>SKOR2<\/jats:italic>\n                    variants, except for case 4, and their impact on protein function. Recently,\n                    <jats:italic>SKOR2<\/jats:italic>\n                    is reported to be associated with Valence\u2010Farazi Cerebellar Ataxia Syndrome (OMIM # 621386) (\n                    <jats:italic>Skor2<\/jats:italic>\n                    \u2014\n                    <jats:italic>OMIM<\/jats:italic>\n                    \u2014\n                    <jats:italic>OMIM.ORG<\/jats:italic>\n                    ). This study expands the phenotypic spectrum for this newly described condition. Additional studies in affected individuals will be needed to refine the phenotypic spectrum and identify genotype\u2013phenotype correlations.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70125","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T06:56:14Z","timestamp":1773384974000},"page":"1725-1739","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biallelic Novel\n                    <scp>\n                      <i>SKOR2<\/i>\n                    <\/scp>\n                    Variants in Individuals With Cerebellar Hypoplasia and Intellectual Disability, Expanding the Phenotypic Spectrum of Valence\u2010Farazi Cerebellar Ataxia Syndrome"],"prefix":"10.1002","volume":"200","author":[{"given":"Aya","family":"Abu\u2010El\u2010Haija","sequence":"first","affiliation":[{"name":"Division of Medical Genetics and Genomics Boston Children's Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Bayat","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Danish Epilepsy Center  Dianalund Denmark"},{"name":"Department of Regional Health Research University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2338-5436","authenticated-orcid":false,"given":"Hanifenur","family":"Manc\u0131lar","sequence":"additional","affiliation":[{"name":"Acibadem Labgen Genetic Diagnosis Center  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1820-9094","authenticated-orcid":false,"given":"Eyyup","family":"Uctepe","sequence":"additional","affiliation":[{"name":"Acibadem Labgen Genetic Diagnosis Center  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma Nisa","family":"Esen","sequence":"additional","affiliation":[{"name":"Acibadem Labgen Genetic Diagnosis Center  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sait","family":"Tumer","sequence":"additional","affiliation":[{"name":"Acibadem Labgen Genetic Diagnosis Center  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00fcbra","family":"Metli","sequence":"additional","affiliation":[{"name":"Kocaeli City Hospital  Kocaeli T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Yesilyurt","sequence":"additional","affiliation":[{"name":"Acibadem Labgen Genetic Diagnosis Center  Istanbul T\u00fcrkiye"},{"name":"Acibadem Maslak Hospital  Istanbul Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami Abou","family":"Jamra","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Leipzig Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seema","family":"Lalani","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0393-6835","authenticated-orcid":false,"given":"Rebecca","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Neurology Lucile Packard Children's Hospital  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Mihalek","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Biotechnology University of Rijeka, Faculty of Medicine  Rijeka Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Redler","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical Faculty and University Hospital D\u00fcsseldorf Heinrich\u2010Heine\u2010University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sureni V.","family":"Mullegama","sequence":"additional","affiliation":[{"name":"GeneDx LLC  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Umair","sequence":"additional","affiliation":[{"name":"Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences Ministry of National Guard Health Affairs (MNGH)  Riyadh Saudi Arabia"},{"name":"Department of Life Sciences, School of Science University of Management and Technology  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8235-9441","authenticated-orcid":false,"given":"Meret","family":"Wegler","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Leipzig Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoaib","family":"Nawaz","sequence":"additional","affiliation":[{"name":"Department of Human Genetics\u2010Precision Medicine Program Sidra Medicine  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiology Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Bodamer","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomics Boston Children's Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Broad Institute of Harvard University and MIT  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700344"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469\u20108749.2008.03224.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1071"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.07.061"},{"key":"e_1_2_8_6_1","unstructured":"Entry Search\u2014Skor2\u2014OMIM\u2014(OMIM.ORG). n.d. 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