{"entity": "journal", "iuid": "11c16930160840d2a4ea2135785f5b98", "timestamp": "2026-07-14T03:56:25.694Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Eur%20J%20Med%20Genet.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Eur%20J%20Med%20Genet"}}, "title": "Eur J Med Genet", "issn": "1878-0849", "issn-l": "1769-7212", "publications_count": 5, "publications": [{"entity": "publication", "iuid": "9769ee1e0cc34f988fe4ea50b0f9f3c5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9769ee1e0cc34f988fe4ea50b0f9f3c5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9769ee1e0cc34f988fe4ea50b0f9f3c5"}}, "title": "The outcome of targeted NGS screening in patients with syndromic forms of sagittal and pansynostosis - IL11RA is an emerging core-gene for pansynostosis.", "authors": [{"family": "Topa", "given": "Alexandra", "initials": "A"}, {"family": "Rohlin", "given": "Anna", "initials": "A"}, {"family": "Andersson", "given": "Mattias K", "initials": "MK"}, {"family": "Fehr", "given": "Andr\u00e9", "initials": "A"}, {"family": "Lovmar", "given": "Lovisa", "initials": "L"}, {"family": "Stenman", "given": "G\u00f6ran", "initials": "G"}, {"family": "K\u00f6lby", "given": "Lars", "initials": "L"}], "type": "journal article", "published": "2022-05-00", "journal": {"title": "Eur J Med Genet", "issn": "1878-0849", "issn-l": "1769-7212", "volume": "65", "issue": "5", "pages": "104476"}, "abstract": "Here, we have studied the prevalence and spectrum of genetic alterations in syndromic forms of sagittal and pansynostosis. Eighteen patients with sagittal synostosis (isolated or combined with other synostoses, except coronal) or pansynostosis were phenotypically assessed by retrospective analysis of medical records, three-dimensional computed tomography skull reconstructions, and registered photos. Patient DNAs were analyzed using a targeted next-generation sequencing (NGS) panel including 63 craniosynostosis (CS) related genes. Pathogenic and likely pathogenic variants were found in 72% of the cases, mainly affecting FGFR2, TWIST1, IL11RA, and SKI. Two patients that were negative at NGS screening - one with a supernumerary marker chromosome with duplication of 15q25.2q26.3 and one with a pathogenic PHEX variant - were identified using microarray and single gene analysis, respectively. The overall diagnostic rate in the cohort was thus 83%. We identified two novel likely pathogenic variants in FGFR2 (NM_022970.3: c.811_812delGGinsCC, p.Gly271Pro) and TWIST1 (NM_000474.3: c.476T > A, p.Leu159His), and a novel variant of unclear phenotypic significance in RUNX2 (NM_001024630.3: c.340G > A, p.Val114Ile) which could suggest a modulatory effect. Notably, we also identified three new patients with pansynostosis and a Crouzon-like phenotype with IL11RA mutation. Targeted NGS using a broad panel of CS-related genes is a simple and powerful tool for detecting pathogenic mutations in patients with syndromic forms of CS and multiple suture involvement, in particular pansynostosis. Our results provide additional evidence of an association between pansynostosis and IL11RA, an emerging core gene for autosomal recessive CS.", "doi": "10.1016/j.ejmg.2022.104476", "pmid": "35331937", "labels": {"National Genomics Infrastructure": "Service", "NGI Short read": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S1769-7212(22)00057-X"}], "notes": [], "created": "2022-08-19T08:37:20.168Z", "modified": "2024-01-16T13:48:36.775Z"}, {"entity": "publication", "iuid": "9ccddd5dd5f34d5da01904719caa4f80", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9ccddd5dd5f34d5da01904719caa4f80.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9ccddd5dd5f34d5da01904719caa4f80"}}, "title": "A novel RAD21 p.(Gln592del) variant expands the clinical description of Cornelia de Lange syndrome type 4 - Review of the literature.", "authors": [{"family": "Gudmundsson", "given": "Sanna", "initials": "S"}, {"family": "Anner\u00e9n", "given": "G\u00f6ran", "initials": "G"}, {"family": "Marcos-Alcalde", "given": "\u00cd\u00f1igo", "initials": "\u00cd"}, {"family": "Wilbe", "given": "Maria", "initials": "M"}, {"family": "Melin", "given": "Malin", "initials": "M", "orcid": "0000-0002-6589-2375", "researcher": {"href": "https://publications.scilifelab.se/researcher/190c3991975c43ec952a81df72292c9a.json"}}, {"family": "G\u00f3mez-Puertas", "given": "Paulino", "initials": "P"}, {"family": "Bondeson", "given": "Marie-Louise", "initials": "ML"}], "type": "case reports", "published": "2019-06-00", "journal": {"volume": "62", "issn": "1878-0849", "issue": "6", "pages": "103526", "title": "Eur J Med Genet", "issn-l": "1769-7212"}, "abstract": "Cornelia de Lange syndrome (CdLS) is a heterogeneous developmental disorder where 70% of clinically diagnosed patients harbor a variant in one of five CdLS associated cohesin proteins. Around 500 variants have been identified to cause CdLS, however only eight different alterations have been identified in the RAD21 gene, encoding the RAD21 cohesin complex component protein that constitute the link between SMC1A and SMC3 within the cohesin ring. We report a 15-month-old boy presenting with developmental delay, distinct CdLS-like facial features, gastrointestinal reflux in early infancy, testis retention, prominent digit pads and diaphragmatic hernia. Exome sequencing revealed a novel RAD21 variant, c.1774_1776del, p.(Gln592del), suggestive of CdLS type 4. Segregation analysis of the two healthy parents confirmed the variant as de novo and bioinformatic analysis predicted the variant as disease-causing. Assessment by in silico structural model predicted that the p.Gln592del variant results in a discontinued contact between RAD21-Lys591 and the SMC1A residues Glu1191 and Glu1192, causing changes in the RAD21-SMC1A interface. In conclusion, we report a patient that expands the clinical description of CdLS type 4 and presents with a novel RAD21 p.(Glu592del) variant that causes a disturbed RAD21-SMC1A interface according to in silco structural modeling.", "doi": "10.1016/j.ejmg.2018.08.007", "pmid": "30125677", "labels": {"Clinical Genomics Uppsala": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S1769-7212(18)30189-7"}], "notes": [], "created": "2018-12-04T10:26:37.835Z", "modified": "2024-01-16T13:48:44.310Z"}, {"entity": "publication", "iuid": "ec5addbe8a004dc9be3de2406c51efeb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ec5addbe8a004dc9be3de2406c51efeb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ec5addbe8a004dc9be3de2406c51efeb"}}, "title": "Cenani-Lenz syndrome restricted to limb and kidney anomalies associated with a novel LRP4 missense mutation.", "authors": [{"family": "Khan", "given": "Tahir Naeem", "initials": "TN"}, {"family": "Klar", "given": "J", "initials": "J"}, {"family": "Ali", "given": "Zafar", "initials": "Z"}, {"family": "Khan", "given": "F", "initials": "F"}, {"family": "Baig", "given": "S M", "initials": "SM"}, {"family": "Dahl", "given": "N", "initials": "N"}], "type": "case reports", "published": "2013-07-00", "journal": {"volume": "56", "issn": "1878-0849", "issue": "7", "pages": "371-374", "title": "Eur J Med Genet", "issn-l": "1769-7212"}, "abstract": "Cenani-Lenz syndrome (CLS) is a rare autosomal recessive developmental disorder of the limbs. The disorder is characterized by complete syndactyly with metacarpal fusions and/or oligodactyly sometimes accompanied by radioulnar synostosis. The clinical expression is variable and kidney agenesis/hypoplasia, craniofacial dysmorphism and teeth abnormalities are frequent features as well as lower limb involvement. CLS was recently associated with mutations in the low-density lipoprotein receptor-related protein 4 (LRP4) gene and dysregulated canonical WNT signaling. We have identified a large consanguineous Pakistani pedigree with 9 members affected by CLS. The affected individuals present with a consistent expression of the syndrome restricted to the limbs and kidneys. Symptoms from the lower limb are mild or absent and there were no radioulnar synostosis or craniofacial involvement. Genetic analysis using autozygosity mapping and sequencing revealed homozygosity for a novel missense mutation c.2858T\u00a0>\u00a0C (p.L953P) in the LRP4 gene. The mutation is located in a region encoding the highly conserved low-density lipoprotein receptor repeat class B domain of LRP4. Our findings add to the genotype-phenotype correlations in CLS and support kidney anomalies as a frequent associated feature.", "doi": "10.1016/j.ejmg.2013.04.007", "pmid": "23664847", "labels": {"National Genomics Infrastructure": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "S1769-7212(13)00091-8"}], "notes": [], "created": "2017-05-04T14:57:53.417Z", "modified": "2020-01-21T13:56:06.007Z"}, {"entity": "publication", "iuid": "13d3b764ad5e4bf282c6a1e3b541162d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/13d3b764ad5e4bf282c6a1e3b541162d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/13d3b764ad5e4bf282c6a1e3b541162d"}}, "title": "Unbalanced translocation 9;16 in two children with dysmorphic features, and severe developmental delay: Evidence of cross-over within derivative chromosome 9 in patient #1.", "authors": [{"family": "Zambrano", "given": "Regina M", "initials": "RM"}, {"family": "Wohler", "given": "Elizabeth", "initials": "E"}, {"family": "Anner\u00e9n", "given": "G\u00f6ran", "initials": "G"}, {"family": "Thuresson", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Cutting", "given": "Garry R", "initials": "GR"}, {"family": "Batista", "given": "Denise A", "initials": "DA"}], "type": "case reports", "published": "2010-12-07", "journal": {"volume": "54", "issn": "1878-0849", "issue": "2", "pages": "189-193", "title": "Eur J Med Genet", "issn-l": "1769-7212"}, "abstract": "We describe 2 children with dysmorphic features, and severe developmental delay presenting with overlapping unbalanced translocations of 9q34.3 and 16p13. Patient #1: A 4 year old African-American female with normal karyotype with a pericentric inversion on one chromosome 9 known to be a benign variant. Low resolution array CGH revealed a single BAC clone loss at 9q34.3 and a single BAC clone gain at 16p13.3, confirmed by FISH. Whole genome SNP array analysis refined these findings, identifying a terminal 1.28 Mb deletion (138,879,862-140,164,310) of 9q34.3 and a terminal 1.62 Mb duplication (45,320-1,621,753) of 16p13.3. Sub-telomeric FISH showed an unbalanced cryptic translocation involving the inverted chromosome 9 and chromosome 16. FISH of the father showed a balanced t(9;16)(q34.3;p13.3) involving the non-inverted chromosome 9, and a pericentric inversion on the normal 9 homologous chromosome. The presence of two rearrangements on chromosome 9, both an unbalanced translocation and a pericentric inversion, indicates recombination between the inverted and derivative 9 homologues from her father. Patient #2: A 1 year old Iraqi-Moroccan female with normal karyotype. Array-CGH identified a 0.56 Mb deletion of 9q34.3 (139,586,637-140,147,760) and an 11.31 Mb duplication of 16p13.3p13.13 (31,010-11,313,519). Maternal FISH showed a balanced t(9;16)(q34.3;p13.13). Both patients present with similar clinical phenotype.", "doi": "10.1016/j.ejmg.2010.11.008", "pmid": "21144914", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "S1769-7212(10)00140-0"}], "notes": [], "created": "2017-05-04T15:01:57.557Z", "modified": "2020-01-21T13:56:00.839Z"}, {"entity": "publication", "iuid": "1bd62d3b4fc04ffdb1f82baffda989e0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1bd62d3b4fc04ffdb1f82baffda989e0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1bd62d3b4fc04ffdb1f82baffda989e0"}}, "title": "Investigation of gene dosage imbalances in patients with Noonan syndrome using multiplex ligation-dependent probe amplification analysis.", "authors": [{"family": "Nystr\u00f6m", "given": "Anna-Maja", "initials": "AM"}, {"family": "Ekvall", "given": "Sara", "initials": "S"}, {"family": "Thuresson", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Denayer", "given": "Ellen", "initials": "E"}, {"family": "Legius", "given": "Eric", "initials": "E"}, {"family": "Kamali-Moghaddam", "given": "Masood", "initials": "M", "orcid": "0000-0002-1303-2218", "researcher": {"href": "https://publications.scilifelab.se/researcher/290dd535fb414c68bc49a8a2b7995770.json"}}, {"family": "Westermark", "given": "Bengt", "initials": "B"}, {"family": "Anner\u00e9n", "given": "G\u00f6ran", "initials": "G"}, {"family": "Bondeson", "given": "Marie-Louise", "initials": "ML"}], "type": "journal article", "published": "2010-03-17", "journal": {"volume": "53", "issn": "1878-0849", "issue": "3", "pages": "117-121", "title": "Eur J Med Genet", "issn-l": "1769-7212"}, "abstract": "The RAS-MAPK syndromes are a group of clinically and genetically related disorders caused by dysregulation of the RAS-MAPK pathway. A member of this group of disorders, Noonan syndrome (NS), is associated with several different genes within the RAS-MAPK pathway. To date, mutations in PTPN11, SOS1, KRAS, RAF1 and SHOC2 are known to cause NS and a small group of patients harbour mutations in BRAF, MEK1 or NRAS. The majority of the mutations are predicted to cause an up-regulation of the pathway; hence they are gain-of-function mutations. Despite recent advances in gene identification in NS, the genetic aetiology is still unknown in about 1/4 of patients. To investigate the contribution of gene dosage imbalances of RAS-MAPK-related genes to the pathogenesis of NS, a multiplex ligation-dependent probe amplification (MLPA) assay was developed. Two probe sets were designed for seven RAS-MAPK-syndrome-related candidate genes: PTPN11, SOS1, RAF1, KRAS, BRAF, MEK1 and MEK2. The probe sets were validated in 15 healthy control individuals and in glioma tumour cell lines. Subsequently, 44 NS patients negative for mutations in known NS-associated genes were screened using the two probe sets. The MLPA results for the patients revealed no gene dosage imbalances. In conclusion, the present results exclude copy number variation of PTPN11, SOS1, RAF1, KRAS, BRAF, MEK1 and MEK2 as a common pathogenic mechanism of NS. The validated and optimised RAS-MAPK probe sets presented here enable rapid high throughput screening of further patients with RAS-MAPK syndromes.", "doi": "10.1016/j.ejmg.2010.03.001", "pmid": "20302979", "labels": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "S1769-7212(10)00017-0"}], "notes": [], "created": "2017-05-04T15:01:51.981Z", "modified": "2021-07-08T10:16:52.805Z"}], "created": "2017-05-09T09:12:06.653Z", "modified": "2020-11-27T13:14:07.739Z"}