{"entity": "researcher", "timestamp": "2026-09-23T21:38:31.667Z", "family": "Carvalho", "given": "Claudia M B", "initials": "CMB", "orcid": "0000-0002-2090-298X", "affiliations": ["Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.", "Pacific Northwest Research Institute (PNRI), Seattle, Washington, USA."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/957f6ddd88b24cf3aee597cf2095ec56.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/957f6ddd88b24cf3aee597cf2095ec56"}}, "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": "ae099c48ae1a48d3b15f364265c1c073", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ae099c48ae1a48d3b15f364265c1c073.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ae099c48ae1a48d3b15f364265c1c073"}}, "title": "Comprehensive structural variation genome map of individuals carrying complex chromosomal rearrangements.", "authors": [{"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Pettersson", "given": "Maria", "initials": "M", "orcid": "0000-0003-3120-1625", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/12ccdc228a31454b8d43136e9708350b.json"}}, {"family": "Vezzi", "given": "Francesco", "initials": "F", "orcid": "0000-0002-0243-0018", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec1f9d0b4a524885b29fb96600d879f7.json"}}, {"family": "Wincent", "given": "Josephine", "initials": "J"}, {"family": "K\u00e4ller", "given": "Max", "initials": "M", "orcid": "0000-0001-6813-3051", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bbbf41bd13c347898cc7fa0cedd4e6b2.json"}}, {"family": "Gruselius", "given": "Joel", "initials": "J"}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/49e071495ddf43e5b570dfb22c1fec06.json"}}, {"family": "Syk Lundberg", "given": "Elisabeth", "initials": "E"}, {"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": "2019-02-00", "journal": {"title": "PLoS Genet", "issn": "1553-7404", "volume": "15", "issue": "2", "pages": "e1007858", "issn-l": "1553-7390"}, "abstract": "Complex chromosomal rearrangements (CCRs) are rearrangements involving more than two chromosomes or more than two breakpoints. Whole genome sequencing (WGS) allows for outstanding high resolution characterization on the nucleotide level in unique sequences of such rearrangements, but problems remain for mapping breakpoints in repetitive regions of the genome, which are known to be prone to rearrangements. Hence, multiple complementary WGS experiments are sometimes needed to solve the structures of CCRs. We have studied three individuals with CCRs: Case 1 and Case 2 presented with de novo karyotypically balanced, complex interchromosomal rearrangements (46,XX,t(2;8;15)(q35;q24.1;q22) and 46,XY,t(1;10;5)(q32;p12;q31)), and Case 3 presented with a de novo, extremely complex intrachromosomal rearrangement on chromosome 1. Molecular cytogenetic investigation revealed cryptic deletions in the breakpoints of chromosome 2 and 8 in Case 1, and on chromosome 10 in Case 2, explaining their clinical symptoms. In Case 3, 26 breakpoints were identified using WGS, disrupting five known disease genes. All rearrangements were subsequently analyzed using optical maps, linked-read WGS, and short-read WGS. In conclusion, we present a case series of three unique de novo CCRs where we by combining the results from the different technologies fully solved the structure of each rearrangement. The power in combining short-read WGS with long-molecule sequencing or optical mapping in these unique de novo CCRs in a clinical setting is demonstrated.", "doi": "10.1371/journal.pgen.1007858", "pmid": "30735495", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6368290"}, {"db": "pii", "key": "PGENETICS-D-18-00854"}], "notes": [], "created": "2026-09-23T09:25:53.119Z", "modified": "2026-09-23T09:25:53.290Z"}, {"entity": "publication", "iuid": "461b01d874124d3c9963a3c1537e2201", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/461b01d874124d3c9963a3c1537e2201.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/461b01d874124d3c9963a3c1537e2201"}}, "title": "Alu-Alu mediated intragenic duplications in IFT81 and MATN3 are associated with skeletal dysplasias.", "authors": [{"family": "Pettersson", "given": "Maria", "initials": "M", "orcid": "0000-0003-3120-1625", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/12ccdc228a31454b8d43136e9708350b.json"}}, {"family": "Vaz", "given": "Raquel", "initials": "R"}, {"family": "Hammarsj\u00f6", "given": "Anna", "initials": "A"}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J", "orcid": "0000-0003-3716-4917", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/83d05cbf798f4b48800dc89b57427cf2.json"}}, {"family": "Carvalho", "given": "Claudia M B", "initials": "CMB", "orcid": "0000-0002-2090-298X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/957f6ddd88b24cf3aee597cf2095ec56.json"}}, {"family": "Hofmeister", "given": "Wolfgang", "initials": "W", "orcid": "0000-0002-6306-9262", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dcb0e7b621694cc3bed0505b0cddcaf4.json"}}, {"family": "Tham", "given": "Emma", "initials": "E"}, {"family": "Horemuzova", "given": "Eva", "initials": "E"}, {"family": "Voss", "given": "Ulrika", "initials": "U"}, {"family": "Nishimura", "given": "Gen", "initials": "G"}, {"family": "Klintberg", "given": "Bo", "initials": "B"}, {"family": "Nordgren", "given": "Ann", "initials": "A"}, {"family": "Nilsson", "given": "Daniel", "initials": "D"}, {"family": "Grigelioniene", "given": "Giedre", "initials": "G"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d28fb4cc61f4033b2ac525fed3d6b94.json"}}], "type": "case reports", "published": "2018-10-00", "journal": {"title": "Hum. Mutat.", "issn": "1098-1004", "volume": "39", "issue": "10", "pages": "1456-1467", "issn-l": "1059-7794"}, "abstract": "Skeletal dysplasias are a diverse group of rare Mendelian disorders with clinical and genetic heterogeneity. Here, we used targeted copy number variant (CNV) screening and identified intragenic exonic duplications, formed through Alu-Alu fusion events, in two individuals with skeletal dysplasia and negative exome sequencing results. First, we detected a homozygous tandem duplication of exon 9 and 10 in IFT81 in a boy with Jeune syndrome, or short-rib thoracic dysplasia (SRTD) (MIM# 208500). Western blot analysis did not detect any wild-type IFT81 protein in fibroblasts from the patient with the IFT81 duplication, but only a shorter isoform of IFT81 that was also present in the normal control samples. Complementary zebrafish studies suggested that loss of full-length IFT81 protein but expression of a shorter form of IFT81 protein affects the phenotype while being compatible with life. Second, a de novo tandem duplication of exons 2 to 5 in MATN3 was identified in a girl with multiple epiphyseal dysplasia (MED) type 5 (MIM# 607078). Our data highlights the importance of detection and careful characterization of intragenic duplication CNVs, presenting them as a novel and very rare genetic mechanism in IFT81-related Jeune syndrome and MATN3-related MED.", "doi": "10.1002/humu.23605", "pmid": "30080953", "labels": [], "xrefs": [], "notes": [], "created": "2026-09-23T11:55:46.143Z", "modified": "2026-09-23T11:55:46.213Z"}]}