{"entity": "researcher", "timestamp": "2026-09-23T21:52:34.065Z", "family": "Lupski", "given": "James R", "initials": "JR", "orcid": "0000-0001-9907-9246", "affiliations": ["Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.", "Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.", "Texas Children's Hospital, Houston, Texas, USA.", "Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/d7abcaff111c4272ac9347d97a4b520d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/d7abcaff111c4272ac9347d97a4b520d"}}, "publications": [{"entity": "publication", "iuid": "cb4e4e8aaf014ad2aa895854196248b3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cb4e4e8aaf014ad2aa895854196248b3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cb4e4e8aaf014ad2aa895854196248b3"}}, "title": "Novel pathogenic genomic variants leading to autosomal dominant and recessive Robinow syndrome.", "authors": [{"family": "Zhang", "given": "Chaofan", "initials": "C", "orcid": "0000-0003-0504-5999", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/541531103b3e4ffc802be0073482cb6a.json"}}, {"family": "Mazzeu", "given": "Juliana F", "initials": "JF", "orcid": "0000-0002-6161-0510", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d988b145c3e147588b67b85fb994e0bb.json"}}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Grochowski", "given": "Christopher M", "initials": "CM", "orcid": "0000-0002-3884-7720", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/88a70acbf92744869c3e9c067f5278a6.json"}}, {"family": "White", "given": "Janson", "initials": "J"}, {"family": "Akdemir", "given": "Zeynep C", "initials": "ZC"}, {"family": "Jhangiani", "given": "Shalini N", "initials": "SN"}, {"family": "Muzny", "given": "Donna M", "initials": "DM"}, {"family": "Gibbs", "given": "Richard A", "initials": "RA", "orcid": "0000-0002-1356-5698", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cc9f89d4859042c49cca44bbcd01c92e.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A"}, {"family": "Lupski", "given": "James R", "initials": "JR", "orcid": "0000-0001-9907-9246", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d7abcaff111c4272ac9347d97a4b520d.json"}}, {"family": "Sutton", "given": "V Reid", "initials": "VR"}, {"family": "Carvalho", "given": "Claudia M B", "initials": "CMB", "orcid": "0000-0002-2090-298X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/957f6ddd88b24cf3aee597cf2095ec56.json"}}], "type": "journal article", "published": "2021-12-00", "journal": {"title": "Am. J. Med. Genet. A", "issn": "1552-4833", "volume": "185", "issue": "12", "pages": "3593-3600", "issn-l": "1552-4825"}, "abstract": "Robinow syndrome (RS) is a genetically heterogeneous disorder characterized by skeletal dysplasia and a distinctive facial appearance. Previous studies have revealed locus heterogeneity with rare variants in DVL1, DVL3, FZD2, NXN, ROR2, and WNT5A underlying the etiology of RS. The aforementioned \"Robinow-associated genes\" and their gene products all play a role in the WNT/planar cell polarity signaling pathway. We performed gene-targeted Sanger sequencing, exome sequencing, genome sequencing, and array comparative genomic hybridization on four subjects with a clinical diagnosis of RS who had not had prior DNA testing. Individuals in our cohort were found to carry pathogenic or likely pathogenic variants in three RS related genes: DVL1, ROR2, and NXN. One subject was found to have a nonsense variant (c.817C > T [p.Gln273*]) in NXN in trans with an ~1 Mb telomeric deletion on chromosome 17p containing NXN, which supports our contention that biallelic NXN variant alleles are responsible for a novel autosomal recessive RS locus. These findings provide increased understanding of the role of WNT signaling in skeletal development and maintenance. These data further support the hypothesis that dysregulation of the noncanonical WNT pathway in humans gives rise to RS.", "doi": "10.1002/ajmg.a.61908", "pmid": "33048444", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1735294"}, {"db": "pmc", "key": "PMC8445516"}], "notes": [], "created": "2026-09-23T08:49:15.112Z", "modified": "2026-09-23T08:49:15.407Z"}, {"entity": "publication", "iuid": "5ac05fc995b94fcb937c49c3025a5dd1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5ac05fc995b94fcb937c49c3025a5dd1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5ac05fc995b94fcb937c49c3025a5dd1"}}, "title": "Cytogenetically visible inversions are formed by multiple molecular mechanisms.", "authors": [{"family": "Pettersson", "given": "Maria", "initials": "M", "orcid": "0000-0003-3120-1625", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/12ccdc228a31454b8d43136e9708350b.json"}}, {"family": "Grochowski", "given": "Christopher M", "initials": "CM", "orcid": "0000-0002-3884-7720", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/88a70acbf92744869c3e9c067f5278a6.json"}}, {"family": "Wincent", "given": "Josephine", "initials": "J"}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J", "orcid": "0000-0003-3716-4917", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/83d05cbf798f4b48800dc89b57427cf2.json"}}, {"family": "Breman", "given": "Amy M", "initials": "AM"}, {"family": "Cheung", "given": "Sau W", "initials": "SW"}, {"family": "Krepischi", "given": "Ana C V", "initials": "ACV"}, {"family": "Rosenberg", "given": "Carla", "initials": "C"}, {"family": "Lupski", "given": "James R", "initials": "JR", "orcid": "0000-0001-9907-9246", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d7abcaff111c4272ac9347d97a4b520d.json"}}, {"family": "Ottosson", "given": "Jesper", "initials": "J"}, {"family": "Lovmar", "given": "Lovisa", "initials": "L"}, {"family": "Gacic", "given": "Jelena", "initials": "J"}, {"family": "Lundberg", "given": "Elisabeth S", "initials": "ES"}, {"family": "Nilsson", "given": "Daniel", "initials": "D"}, {"family": "Carvalho", "given": "Claudia M B", "initials": "CMB", "orcid": "0000-0002-2090-298X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/957f6ddd88b24cf3aee597cf2095ec56.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d28fb4cc61f4033b2ac525fed3d6b94.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "Hum. Mutat.", "issn": "1098-1004", "volume": "41", "issue": "11", "pages": "1979-1998", "issn-l": "1059-7794"}, "abstract": "Cytogenetically detected inversions are generally assumed to be copy number and phenotypically neutral events. While nonallelic homologous recombination is thought to play a major role, recent data suggest the involvement of other molecular mechanisms in inversion formation. Using a combination of short-read whole-genome sequencing (WGS), 10X Genomics Chromium WGS, droplet digital polymerase chain reaction and array comparative genomic hybridization we investigated the genomic structure of 18 large unique cytogenetically detected chromosomal inversions and achieved nucleotide resolution of at least one chromosomal inversion junction for 13/18 (72%). Surprisingly, we observed that seemingly copy number neutral inversions can be accompanied by a copy-number gain of up to 350 kb and local genomic complexities (3/18, 17%). In the resolved inversions, the mutational signatures are consistent with nonhomologous end-joining (8/13, 62%) or microhomology-mediated break-induced replication (5/13, 38%). Our study indicates that short-read 30x coverage WGS can detect a substantial fraction of chromosomal inversions. Moreover, replication-based mechanisms are responsible for approximately 38% of those events leading to a significant proportion of inversions that are actually accompanied by additional copy-number variation potentially contributing to the overall phenotypic presentation of those patients.", "doi": "10.1002/humu.24106", "pmid": "32906200", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7702065"}], "notes": [], "created": "2026-09-23T10:09:21.042Z", "modified": "2026-09-23T10:47:38.791Z"}, {"entity": "publication", "iuid": "d1a212469ae24b29925e13c685d3169d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d1a212469ae24b29925e13c685d3169d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d1a212469ae24b29925e13c685d3169d"}}, "title": "Whole-genome sequencing reveals complex chromosome rearrangement disrupting NIPBL in infant with Cornelia de Lange syndrome.", "authors": [{"family": "Plesser Duvdevani", "given": "Morasha", "initials": "M"}, {"family": "Pettersson", "given": "Maria", "initials": "M", "orcid": "0000-0003-3120-1625", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/12ccdc228a31454b8d43136e9708350b.json"}}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Avraham", "given": "Ortal", "initials": "O"}, {"family": "Dagan", "given": "Judith", "initials": "J"}, {"family": "Frumkin", "given": "Ayala", "initials": "A", "orcid": "0000-0001-9103-9717", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e81485e1b68848dcb54c39578dbbca6d.json"}}, {"family": "Lupski", "given": "James R", "initials": "JR", "orcid": "0000-0001-9907-9246", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d7abcaff111c4272ac9347d97a4b520d.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A"}, {"family": "Harel", "given": "Tamar", "initials": "T", "orcid": "0000-0003-3595-7075", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c2ea660e75084ede891c75c802ea8a29.json"}}], "type": "case reports", "published": "2020-05-00", "journal": {"title": "Am. J. Med. Genet. A", "issn": "1552-4833", "volume": "182", "issue": "5", "pages": "1143-1151", "issn-l": "1552-4825"}, "abstract": "Clinical laboratory diagnostic evaluation of the genomes of children with suspected genetic disorders, including chromosomal microarray and exome sequencing, cannot detect copy number neutral genomic rearrangements such as inversions, balanced translocations, and complex chromosomal rearrangements (CCRs). We describe an infant with a clinical diagnosis of Cornelia de Lange syndrome (CdLS) in whom chromosome analysis revealed a de novo complex balanced translocation, 46,XY,t(5;7;6)(q11.2;q32;q13)dn. Subsequent molecular characterization by whole-genome sequencing (WGS) identified 23 breakpoints, delineating segments derived from four chromosomes (5;6;7;21) in ancestral or inverted orientation. One of the breakpoints disrupted a known CdLS gene, NIPBL. Further investigation revealed paternal origin of the CCR allele, clustering of the breakpoint junctions, and molecular repair signatures suggestive of a single catastrophic event. Notably, very short DNA segments (25 and 41 bp) were included in the reassembled chromosomes, lending additional support that the DNA repair machinery can detect and repair such segments. Interestingly, there was an independent paternally derived miniscule complex rearrangement, possibly predisposing to subsequent genomic instability. In conclusion, we report a CCR causing a monogenic Mendelian disorder, urging WGS analysis of similar unsolved cases with suspected Mendelian disorders. Breakpoint analysis allowed for identification of the underlying molecular diagnosis and implicated chromoanagenesis in CCR formation.", "doi": "10.1002/ajmg.a.61539", "pmid": "32125084", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1625907"}, {"db": "pmc", "key": "PMC7502196"}], "notes": [], "created": "2026-09-23T10:11:29.263Z", "modified": "2026-09-23T10:49:45.981Z"}]}