{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T05:07:34Z","timestamp":1779512854767,"version":"3.53.1"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Poretti\u2010Boltshauser syndrome (PBS) is an autosomal recessive disorder caused by biallelic pathogenic variants in the\n                      <jats:italic>LAMA1<\/jats:italic>\n                      gene, typically presenting with cerebellar dysplasia and fourth ventricle abnormalities. While neurological and ocular manifestations are well recognized, an association between\n                      <jats:italic>LAMA1<\/jats:italic>\n                      variants and central nervous system (CNS) dysmyelination has not been previously established, and the underlying mechanisms remain unexplored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Presentation<\/jats:title>\n                    <jats:p>\n                      We report two pediatric siblings from a single family with novel compound heterozygous\n                      <jats:italic>LAMA1<\/jats:italic>\n                      variants [c.505C&gt;T (p.Arg169Ter) and c.634del (p.Ser212HisfsTer28)]. Both patients presented with classic PBS features including ataxia, developmental delay, and oculomotor apraxia. Neuroimaging confirmed cerebellar dysplasia and fourth ventricle abnormalities. Notably, we observed the unexpected concurrence of cerebral white matter hypomyelination, a finding rarely associated with PBS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This report presents the first clinical evidence linking novel\n                      <jats:italic>LAMA1<\/jats:italic>\n                      variants to cerebral hypomyelination in PBS, based on the concordant observation in two affected siblings from the same family. Its specific association with\n                      <jats:italic>LAMA1<\/jats:italic>\n                      \u2010related PBS had not been clearly delineated previously. Drawing on insights from the literature, we hypothesize that LAMA1 dysfunction may disrupt key stages of oligodendrocyte precursor cell biology, specifically survival, proliferation, migration, and differentiation, providing a potential mechanistic basis for the CNS hypomyelination observed in our patients. These findings expand both the phenotypic and genotypic spectrum associated with\n                      <jats:italic>LAMA1<\/jats:italic>\n                      mutations and offer new insights into possible mechanisms of CNS hypomyelination in PBS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70225","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T16:14:01Z","timestamp":1777306441000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel\n                    <scp>LAMA1<\/scp>\n                    Mutations in a Pedigree With Poretti\u2010Boltshauser Syndrome: Implications for Hypomyelination"],"prefix":"10.1002","volume":"14","author":[{"given":"Si","family":"Huang","sequence":"first","affiliation":[{"name":"Foshan Fosun Chancheng Hospital  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Li","sequence":"additional","affiliation":[{"name":"The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xin","sequence":"additional","affiliation":[{"name":"Foshan Fosun Chancheng Hospital  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Mo","sequence":"additional","affiliation":[{"name":"Foshan Fosun Chancheng Hospital  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuwen","family":"Lin","sequence":"additional","affiliation":[{"name":"Foshan Fosun Chancheng Hospital  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingbin","family":"Mai","sequence":"additional","affiliation":[{"name":"Foshan Fosun Chancheng Hospital  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbin","family":"He","sequence":"additional","affiliation":[{"name":"Foshan Fosun Chancheng Hospital  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Zhong","sequence":"additional","affiliation":[{"name":"Foshan Fosun Chancheng Hospital  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Xu","sequence":"additional","affiliation":[{"name":"Foshan Fosun Chancheng Hospital  Foshan Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.07.007"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/2023.03.06.531347"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.4161\/cam.22826"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.948517"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.4161\/cam.21831"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24117"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbx106"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13241"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.19"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina61050881"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab163"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22365"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1042403"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.TEA.2009.0837"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201056488\u20107"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102015\u2010103416"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.644947"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.952135"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010016\u20102381\u20100"}],"container-title":["Molecular Genetics &amp; 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