{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T11:13:42Z","timestamp":1789298022492,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    LAMA2\u2010related dystrophies (LAMA2\u2010RD) constitute a rare neuromuscular disorder with a broad spectrum of phenotypic severity. Our understanding of the genotype\u2013phenotype correlations in this condition remains incomplete, and reliable clinical data for clinical trial readiness is limited. In this retrospective study, we reviewed the genetic data and medical records of 114 LAMA2\u2010RD patients enrolled at seven research centers in Brazil. We identified 58 different pathogenic variants, including 21 novel ones. Six variants were more prevalent and were present in 81.5% of the patients. Notably, the c.1255del, c.2049_2050del, c.3976 C&gt;T, c.5234+1G&gt;A, and c.4739dup variants were found in patients unable to walk and without cortical malformation. In contrast, the c.2461A&gt;C variant was present in patients who could walk unassisted. Among ambulatory patients, missense variants were more prevalent (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Although no specific hotspot regions existed in the\n                    <jats:italic>LAMA2<\/jats:italic>\n                    , 51% of point mutations were in the LN domain, and 88% of the missense variants were found within this domain. Functional analysis was performed in one intronic variant (c.4960\u201017C&gt;A) and revealed an out\u2010of\u2010frame transcript, indicating that the variant creates a cryptic splicing site (AG). Our study has shed light on crucial phenotype\u2013genotype correlations and provided valuable insights, particularly regarding the Latin American population.\n                  <\/jats:p>","DOI":"10.1111\/cge.14538","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T05:44:28Z","timestamp":1715751868000},"page":"305-314","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic profile of Brazilian patients with\n                    <scp>LAMA2<\/scp>\n                    \u2010related dystrophies"],"prefix":"10.1111","volume":"106","author":[{"given":"Clara Gontijo","family":"Camelo","sequence":"first","affiliation":[{"name":"Department of Neurology Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP)  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiane de Araujo Martins","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Neurology Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP)  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana da Cunha","family":"Artilheiro","sequence":"additional","affiliation":[{"name":"Department of Neurology Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP)  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alulin T\u00e1cio Quadros Monteiro","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Department of Neurology Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP)  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Gurgel Gianetti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Universidade Federal de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Vin\u00edcius","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Funda\u00e7\u00e3o Hospitalar do Estado de Minas Gerais  Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina Carvalho","family":"Donis","sequence":"additional","affiliation":[{"name":"Medical Genetics Division and Neurology Division Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1141-6573","authenticated-orcid":false,"given":"Jonas Alex Morales","family":"Saute","sequence":"additional","affiliation":[{"name":"Medical Genetics Division and Neurology Division Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Pessoa","sequence":"additional","affiliation":[{"name":"Children's Hospital Albert Sabin  Fortaleza Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"H\u00e9lio","family":"Van der Linden","sequence":"additional","affiliation":[{"name":"Rehabilitation Center Dr. Henrique Santillo  Goi\u00e2nia Brazil"},{"name":"Neurology Institute of Goi\u00e2nia  Goi\u00e2nia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Rita Alc\u00e2ntara","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica Jacinto Magalh\u00e3es Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio (CHUdSA)  Porto Portugal"},{"name":"UMIB\u2013Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2013School of Medicine and Biomedical Sciences University of Porto  Porto Portugal"},{"name":"ITR\u2013Laboratory for Integrative and Translational Research in Population Health  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2236-3956","authenticated-orcid":false,"given":"Leslie Domenici","family":"Kulikowski","sequence":"additional","affiliation":[{"name":"Department of Neurology Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP)  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Kok","sequence":"additional","affiliation":[{"name":"Department of Neurology Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP)  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmar","family":"Zanoteli","sequence":"additional","affiliation":[{"name":"Department of Neurology Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP)  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(99)00055-3"},{"issue":"4","key":"e_1_2_10_3_1","first-page":"351","article-title":"Congenital muscular dystrophy with merosin deficiency","volume":"317","author":"Tome FM","year":"1994","journal-title":"C R Acad Sci III"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0004-282X2009000100038"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001303"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.10.649"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2013.12.011"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-004-1398-y"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-221638"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2010.02.001"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23599"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-140031"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-01950-x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12366"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2020.03.009"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctm.2015.05.002"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2019.00305"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-33098-3"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)65402-5"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2014.11.005"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16493"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2023.01.017"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2021.07.009"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51172"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2018.01.005"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.22132"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2014.09.010"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2008.01068.x"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14538","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T22:13:17Z","timestamp":1723500797000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,15]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1111\/cge.14538"],"URL":"https:\/\/doi.org\/10.1111\/cge.14538","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14538\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14538\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14538\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14538\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14538\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,15]]},"assertion":[{"value":"2024-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}