{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:42:15Z","timestamp":1791999735811,"version":"4.4.0"},"reference-count":22,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alazami syndrome is a rare disorder with an autosomal recessive inheritance caused by pathogenic biallelic variants in the LARP7 gene. Clinically, it is mainly characterized by short stature, intellectual disability, and dysmorphic facial features. However, the phenotype is not yet well-defined because less than 50 cases have been described to date. Here, we report three new patients from two unrelated Spanish families who, in addition to the defined features of Alazami syndrome, also exhibit unique features that broaden the phenotypic spectrum of the syndrome. Moreover, we describe the novel frameshift variant c.690_699delins27 in the LARP7 gene, in which loss of function is a known mechanism of Alazami syndrome.<\/jats:p>","DOI":"10.1055\/a-1947-8411","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T23:51:12Z","timestamp":1663717872000},"page":"031-036","source":"Crossref","is-referenced-by-count":5,"title":["Expanding the Phenotypic Spectrum of Alazami Syndrome: Two Unrelated Spanish Families"],"prefix":"10.1055","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4640-1526","authenticated-orcid":false,"given":"Emma","family":"Soengas-Gonda","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain"},{"name":"Mitochondrial and Neuromuscular Disorders Group, Hospital 12 de Octubre Health Research Institute (imas12), Madrid, Spain"},{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica), 12 de Octubre University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2749-2709","authenticated-orcid":false,"given":"Rub\u00e9n","family":"P\u00e9rez de la Fuente","sequence":"additional","affiliation":[{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica), 12 de Octubre University Hospital, Madrid, Spain"},{"name":"Department of Genetics, 12 de Octubre University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Arteche-L\u00f3pez","sequence":"additional","affiliation":[{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica), 12 de Octubre University Hospital, Madrid, Spain"},{"name":"Department of Genetics, 12 de Octubre University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda de los \u00c1ngeles","family":"G\u00f3mez-Cano","sequence":"additional","affiliation":[{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica), 12 de Octubre University Hospital, Madrid, Spain"},{"name":"Department of Pediatrics, Endocrinology Unit, 12 de Octubre University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Francisco","family":"Quesada-Espinosa","sequence":"additional","affiliation":[{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica), 12 de Octubre University Hospital, Madrid, Spain"},{"name":"Department of Genetics, 12 de Octubre University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Palma Milla","sequence":"additional","affiliation":[{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica), 12 de Octubre University Hospital, Madrid, Spain"},{"name":"Department of Genetics, 12 de Octubre University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Miguel","family":"Lezana Rosales","sequence":"additional","affiliation":[{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica), 12 de Octubre University Hospital, Madrid, Spain"},{"name":"Department of Genetics, 12 de Octubre University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Mayo de Andr\u00e9s","sequence":"additional","affiliation":[{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica), 12 de Octubre University Hospital, Madrid, Spain"},{"name":"Department of Genetics, 12 de Octubre University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Teresa","family":"S\u00e1nchez-Calv\u00edn","sequence":"additional","affiliation":[{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica), 12 de Octubre University Hospital, Madrid, Spain"},{"name":"Department of Genetics, 12 de Octubre University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"G\u00f3mez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica), 12 de Octubre University Hospital, Madrid, Spain"},{"name":"Department of Genetics, 12 de Octubre University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olalla","family":"Sierra Tomillo","sequence":"additional","affiliation":[{"name":"Department of Genetics, 12 de Octubre University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Juarez Rufian","sequence":"additional","affiliation":[{"name":"Department of Genetics, 12 de Octubre University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Ramos Gomez","sequence":"additional","affiliation":[{"name":"Department of Genetics, 12 de Octubre University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Herrero-Forte","sequence":"additional","affiliation":[{"name":"Clinical Genetics, Clinical Analysis Service, Molecular Diagnostics Unit, Institute of Laboratory Medicine (UDM-IML), Clinico San Carlos University Hospital, Madrid, Spain"},{"name":"San Carlos Clinical Research Institute (IdISSC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Fenollar-Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Clinical Genetics, Clinical Analysis Service, Molecular Diagnostics Unit, Institute of Laboratory Medicine (UDM-IML), Clinico San Carlos University Hospital, Madrid, Spain"},{"name":"San Carlos Clinical Research Institute (IdISSC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Cotarelo-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Clinical Genetics, Clinical Analysis Service, Molecular Diagnostics Unit, Institute of Laboratory Medicine (UDM-IML), Clinico San Carlos University Hospital, Madrid, Spain"},{"name":"San Carlos Clinical Research Institute (IdISSC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e1n","family":"Garc\u00eda Ron","sequence":"additional","affiliation":[{"name":"Neuropaediatrics Unit, Child and Adolescent Institute, Clinico San Carlos University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"P\u00e9rez Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Clinico San Carlos University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raluca","family":"Oancea-Ionescu","sequence":"additional","affiliation":[{"name":"Clinical Genetics, Clinical Analysis Service, Molecular Diagnostics Unit, Institute of Laboratory Medicine (UDM-IML), Clinico San Carlos University Hospital, Madrid, Spain"},{"name":"San Carlos Clinical Research Institute (IdISSC), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Moreno-Garc\u00eda","sequence":"additional","affiliation":[{"name":"UDISGEN (Unidad de Dismorfolog\u00eda y Gen\u00e9tica), 12 de Octubre University Hospital, Madrid, Spain"},{"name":"Department of Genetics, 12 de Octubre University Hospital, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2022,12,23]]},"reference":[{"issue":"05","key":"ref1","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.molcel.2008.01.003","article-title":"A La-related protein modulates 7SK snRNP integrity to suppress P-TEFb-dependent transcriptional elongation and tumorigenesis","volume":"29","author":"N He","year":"2008","journal-title":"Mol Cell"},{"issue":"18","key":"ref2","doi-asserted-by":"crossref","first-page":"8715","DOI":"10.1093\/nar\/gkt649","article-title":"Conservation of RNA chaperone activity of the human La-related proteins 4, 6 and 7","volume":"41","author":"R H Hussain","year":"2013","journal-title":"Nucleic Acids Res"},{"issue":"02","key":"ref3","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1080\/15476286.2020.1767952","article-title":"Stabilize and connect: the role of LARP7 in nuclear non-coding RNA metabolism","volume":"18","author":"D Hasler","year":"2021","journal-title":"RNA Biol"},{"issue":"08","key":"ref4","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1039\/C6MB00252H","article-title":"Unraveling the conformational determinants of LARP7 and 7SK small nuclear RNA by theoretical approaches","volume":"12","author":"L Xu","year":"2016","journal-title":"Mol Biosyst"},{"issue":"10","key":"ref5","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1002\/humu.22175","article-title":"Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism","volume":"33","author":"A M Alazami","year":"2012","journal-title":"Hum Mutat"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature10423","article-title":"Deep sequencing reveals 50 novel genes for recessive cognitive disorders","volume":"478","author":"H Najmabadi","year":"2011","journal-title":"Nature"},{"issue":"03","key":"ref7","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.neuron.2015.09.048","article-title":"Genes that affect brain structure and function identified by rare variant analyses of Mendelian neurologic disease","volume":"88","author":"E Karaca","year":"2015","journal-title":"Neuron"},{"issue":"01","key":"ref8","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/ajmg.a.37396","article-title":"Compound heterozygous variants in the LARP7 gene as a cause of Alazami syndrome in a Caucasian female with significant failure to thrive, short stature, and developmental disability","volume":"170A","author":"T T Ling","year":"2016","journal-title":"Am J Med Genet A"},{"issue":"03","key":"ref9","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/jhg.2015.134","article-title":"Broadening the phenotypic spectrum of pathogenic LARP7 variants: two cases with intellectual disability, variable growth retardation and distinct facial features","volume":"61","author":"I HIM Hollink","year":"2016","journal-title":"J Hum Genet"},{"issue":"S 09","key":"ref10","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1186\/s12864-016-3093-4","article-title":"Impaired telomere maintenance in Alazami syndrome patients with LARP7 deficiency","volume":"17","author":"B Holohan","year":"2016","journal-title":"BMC Genomics"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"18014","DOI":"10.1038\/hgv.2018.14","article-title":"Novel compound heterozygous variants in the LARP7 gene in a patient with Alazami syndrome","volume":"5","author":"S Dateki","year":"2018","journal-title":"Hum Genome Var"},{"issue":"03","key":"ref12","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ejmg.2018.07.003","article-title":"LARP7 variants and further delineation of the Alazami syndrome phenotypic spectrum among primordial dwarfisms: 2 sisters","volume":"62","author":"M Imbert-Bouteille","year":"2019","journal-title":"Eur J Med Genet"},{"issue":"01","key":"ref13","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s11033-018-4470-7","article-title":"Comparison of clinical parameters with whole exome sequencing analysis results of autosomal recessive patients; a center experience","volume":"46","author":"M Elmas","year":"2019","journal-title":"Mol Biol Rep"},{"issue":"08","key":"ref14","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1002\/ajmg.a.61189","article-title":"Updating the neurodevelopmental profile of Alazami syndrome: illustrating the role of developmental assessment in rare genetic disorders","volume":"179","author":"M H Wojcik","year":"2019","journal-title":"Am J Med Genet A"},{"issue":"02","key":"ref15","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s10038-019-0682-5","article-title":"Alazami syndrome: the first case of papillary thyroid carcinoma","volume":"65","author":"I Ivanovski","year":"2020","journal-title":"J Hum Genet"},{"issue":"04","key":"ref16","doi-asserted-by":"crossref","first-page":"379","DOI":"10.3390\/genes11040379","article-title":"Compound phenotype due to recessive variants in LARP7 and OTOG genes disclosed by an integrated approach of SNP-array and whole exome sequencing","volume":"11","author":"P Palumbo","year":"2020","journal-title":"Genes (Basel)"},{"issue":"05","key":"ref17","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1002\/ajmg.a.62118","article-title":"Alazami syndrome: report of three Indian patients with phenotypic spectrum from adolescence to adulthood","volume":"185","author":"S Das","year":"2021","journal-title":"Am J Med Genet A"},{"issue":"05","key":"ref18","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1016\/j.molcel.2020.01.001","article-title":"The Alazami syndrome-associated protein LARP7 guides U6 small nuclear RNA modification and contributes to splicing robustness","volume":"77","author":"D Hasler","year":"2020","journal-title":"Mol Cell"},{"issue":"08","key":"ref19","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1002\/ajmg.a.62778","article-title":"Further phenotypic delineation of Alazami syndrome","volume":"188","author":"A Al-Hinai","year":"2022","journal-title":"Am J Med Genet A"},{"issue":"06","key":"ref20","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.anpedi.2010.03.017","article-title":"Valoraci\u00f3n del peso, talla e IMC en ni\u00f1os, adolescentes y adultos jvenes de la Comunidad Aut\u00f3noma de Madrid","volume":"73","author":"D L\u00f3pez De Lara","year":"2010","journal-title":"Ann Pediatr (Paris)"},{"issue":"09","key":"ref21","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"A McKenna","year":"2010","journal-title":"Genome Res"},{"issue":"05","key":"ref23","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"S Richards","year":"2015","journal-title":"Genet Med"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1947-8411.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T08:16:17Z","timestamp":1701072977000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1947-8411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,20]]},"references-count":22,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2023,1,16]]},"published-print":{"date-parts":[[2023,2]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1947-8411","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,9,20]]},"published":{"date-parts":[[2022,9,20]]}}}