{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T01:36:35Z","timestamp":1776648995097,"version":"3.51.2"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"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":["Clinical Genetics"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Deleterious variants in\n                    <jats:italic>COL4A2<\/jats:italic>\n                    , encoding type IV collagen's alpha\u20102 chain, cause heterogeneous cerebrovascular and developmental brain malformations. While many dominant variants are known, biallelic changes are rarely reported. We reported two severe cases: Case #1, an aborted fetus with cerebral calcifications, hemorrhages, periventricular leukomalacia, and cerebellar disruption; and Patient #2, a 2\u2010year\u2010old girl with neurodevelopmental impairment, cortical malformations (frontal schizencephaly, polymicrogyria), and reduced white matter volume. Exome sequencing identified a homozygous missense\n                    <jats:italic>COL4A2<\/jats:italic>\n                    variant in case #1 and compound heterozygous loss\u2010of\u2010function variants (splicing and truncating) in case #2. All variants were rare and predicted to affect protein stability and function\n                    <jats:italic>in silico<\/jats:italic>\n                    . Our cases reinforce the association between biallelic\n                    <jats:italic>COL4A2<\/jats:italic>\n                    variants and brain small vessel disease, expanding the recessive COL4A2\u2010related phenotype to include cortical malformations.\n                  <\/jats:p>","DOI":"10.1111\/cge.70043","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T23:54:22Z","timestamp":1755129262000},"page":"356-362","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biallelic\n                    <i>COL4A2<\/i>\n                    Variants Associated With Brain Small Vessel Disease and Brain Malformations"],"prefix":"10.1111","volume":"109","author":[{"given":"Anees","family":"Muhammad","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences Khyber Medical University  Peshawar 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