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Alport syndrome is genetically heterogeneous with three key genes involved (<jats:italic>COL4A3\u20105<\/jats:italic>) and several transmission patterns, including monogenic X\u2010linked, autosomal recessive\/dominant and digenic. We report a consanguineous family where 13 individuals presented variable features of Alport syndrome including kidney failure on two generations and male\u2010to\u2010male transmission, suggesting autosomal dominant inheritance. <jats:italic>COL4A3\u20105<\/jats:italic> gene panel analysis surprisingly reveals two distinct, confirmed splice\u2010altering variants in <jats:italic>COL4A3<\/jats:italic> (NM_000091.4: c.1150+5G&gt;A and c.4028\u20103C&gt;T) present in homozygous or compound heterozygous state in individuals with kidney failure. This adds a further mode of transmission for Alport syndrome where, in a consanguineous family, the independent segregation of two variants at the same locus may create a pseudodominant transmission pattern. These findings highlight the importance of a molecular diagnosis in Alport syndrome for genetic risk counselling, given the variable modes of inheritance, but also the pitfalls of assuming identity by descent in consanguineous families.<\/jats:p>","DOI":"10.1111\/ahg.12454","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T06:19:40Z","timestamp":1639117180000},"page":"145-152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pseudodominant Alport syndrome caused by pathogenic homozygous and compound heterozygous <i>COL4A3<\/i> splicing variants"],"prefix":"10.1111","volume":"86","author":[{"given":"Maha","family":"Mohamed","sequence":"first","affiliation":[{"name":"Renal Services Newcastle Upon Tyne Hospitals NHS Foundation Trust  Newcastle upon Tyne, NE7 7DN United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Tellez","sequence":"additional","affiliation":[{"name":"Northern Genetics Service Newcastle upon Tyne Hospitals NHS Foundation Trust, Central Parkway  Newcastle upon Tyne NE1 3BZ United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, Faculty of Medicine Medical Center\u2010University of Freiburg, Freiburg, Germany and Medizinische Genetik Mainz  Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9170-1579","authenticated-orcid":false,"given":"Daniel P.","family":"Gale","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, Royal Free Hospital University College London  London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1881-3782","authenticated-orcid":false,"given":"John A.","family":"Sayer","sequence":"additional","affiliation":[{"name":"Renal Services Newcastle Upon Tyne Hospitals NHS Foundation Trust  Newcastle upon Tyne, NE7 7DN United Kingdom"},{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences Newcastle University, Central Parkway  Newcastle upon Tyne, NE1 3BZ United Kingdom"},{"name":"NIHR Newcastle Biomedical Research Centre  Newcastle upon Tyne, NE4 5PL United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1178-7980","authenticated-orcid":false,"given":"Eric","family":"Olinger","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences Newcastle University, Central Parkway  Newcastle upon Tyne, NE1 3BZ United 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