{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:54:08Z","timestamp":1789606448549,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T00:00:00Z","timestamp":1694563200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/01053"],"award-info":[{"award-number":["PI20\/01053"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PMP22\/00049"],"award-info":[{"award-number":["PMP22\/00049"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PMP21\/00063"],"award-info":[{"award-number":["PMP21\/00063"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Lamb\u2013Shaffer Syndrome (LSS; OMIM #616803; ORPHA #313892; ORPHA #313884) is an infrequent genetic disorder that affects multiple aspects of human development especially those related to the development of the nervous system. LSS is caused by variants in the\n                    <jats:italic>SOX5<\/jats:italic>\n                    gene. At the molecular level,\n                    <jats:italic>SOX5<\/jats:italic>\n                    gene encodes for a transcription factor containing a High Mobility Group (HMG) DNA\u2010Binding domain with relevant functions in brain development in different vertebrate species. Clinical features of Lamb\u2013Shaffer syndrome may include intellectual disability, delayed speech and language development, attention deficits, hyperactivity, autism spectrum disorder, visual problems and seizures. Additionally, patients with the syndrome may present distinct facial dimorphism such as a wide mouth with full lips, small chin, broad nasal bridge, and deep\u2010set eyes. Other physical features that have been reported in some patients include short stature, scoliosis, and joint hypermobility. Here, we report the clinical and molecular characterization of a Spanish LSS cohort of new 20 patients and review all the patients published so far which amount for 111 patients. The most frequent features included developmental delay, intellectual disability, visual problems, poor speech development and facial dysmorphic features. Strikingly, pain insensitivity and hypermetropia seems to be more frequent than previously reported, based on the frequency seen in the Spanish cohort. Eighty\u2010three variants have been reported so far, single nucleotide variants (SNV) and copy number variants represent 47% and 53%, respectively, from the total of variants reported. Similarly to previous reports, the majority of the SNVs variants of the novel patients reported herein fall in the HMG domain of the protein. However, new variants, affecting other functional domains, were also detected. In conclusion, LLS is a rare genetic disorder mostly characterized by a wide range of developmental and neurological symptoms. Early diagnosis would allow to start of care programs, clinical follow up, prospective studies and appropriate genetic counseling, to promote clinical and social improvement to have profound lifelong benefits for patients and their families. Further research is needed to better understand the underlying mechanisms of the syndrome related to\n                    <jats:italic>SOX5<\/jats:italic>\n                    haploinsufficiency.\n                  <\/jats:p>","DOI":"10.1111\/cge.14423","type":"journal-article","created":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T07:06:10Z","timestamp":1694588770000},"page":"637-647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Lamb\u2013Shaffer syndrome: 20 Spanish patients and literature review expands the view of neurodevelopmental disorders caused by\n                    <i>SOX5<\/i>\n                    haploinsufficiency"],"prefix":"10.1111","volume":"104","author":[{"given":"Jair","family":"Tenorio\u2010Castano","sequence":"first","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras  Madrid Spain"},{"name":"INGEMM\u2010IdIPAZ, Institute of Medical and Molecular Genetics, Hospital Universitario La Paz  Madrid Spain"},{"name":"ITHACA, European Reference Network  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngela S\u00e1nchez\u2010Algaba","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Primary Care Pediatrician, SERMAS  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Coronado","sequence":"additional","affiliation":[{"name":"Department of Radiology Hospital Universitario La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Rodr\u00edguez\u2010Mart\u00edn","sequence":"additional","affiliation":[{"name":"Instituto Cajal, Consejo Superior de Investigaciones Cient\u00edficas (CSIC)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4115-2065","authenticated-orcid":false,"given":"Alejandro","family":"Parra","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras  Madrid Spain"},{"name":"INGEMM\u2010IdIPAZ, Institute of Medical and Molecular Genetics, Hospital Universitario La Paz  Madrid Spain"},{"name":"ITHACA, European Reference Network  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Pascual","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras  Madrid Spain"},{"name":"INGEMM\u2010IdIPAZ, Institute of Medical and Molecular Genetics, Hospital Universitario La Paz  Madrid Spain"},{"name":"ITHACA, European Reference Network  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Cazalla","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras  Madrid Spain"},{"name":"INGEMM\u2010IdIPAZ, Institute of Medical and Molecular Genetics, Hospital Universitario La Paz  Madrid Spain"},{"name":"ITHACA, European Reference Network  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Gallego","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras  Madrid Spain"},{"name":"INGEMM\u2010IdIPAZ, Institute of Medical and Molecular Genetics, Hospital Universitario La Paz  Madrid Spain"},{"name":"ITHACA, European Reference Network  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Arias","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras  Madrid Spain"},{"name":"INGEMM\u2010IdIPAZ, Institute of Medical and Molecular Genetics, Hospital Universitario La Paz  Madrid Spain"},{"name":"ITHACA, European Reference Network  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6295-5142","authenticated-orcid":false,"given":"Aixa V.","family":"Morales","sequence":"additional","affiliation":[{"name":"Instituto Cajal, Consejo Superior de Investigaciones Cient\u00edficas (CSIC)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juli\u00e1n","family":"Nevado","sequence":"additional","affiliation":[{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras  Madrid Spain"},{"name":"INGEMM\u2010IdIPAZ, Institute of Medical and Molecular Genetics, Hospital Universitario La Paz  Madrid Spain"},{"name":"ITHACA, European Reference Network  Brussels 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Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22037"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr032"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2002-0025"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201600062"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(02)00927-7"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2022075"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806791105"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.12.023"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2010.61"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22240"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110313"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63124"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24309"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-021-00835-9"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.016"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btad290"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.02.049"},{"key":"e_1_2_9_19_1","first-page":"1","article-title":"A 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