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Three small unrelated families segregating the combination of deafness and retinal dystrophy were studied by exome sequencing (ES). The proband of Family 1 was found to be compound heterozygous for NM_004525.3:\n                    <jats:italic>LRP2<\/jats:italic>\n                    : c.5005A\u2009&gt;\u2009G, p.(Asn1669Asp) and c.149C\u2009&gt;\u2009G, p.(Thr50Ser). In Family 2, two sisters were found to be compound heterozygous for\n                    <jats:italic>LRP2<\/jats:italic>\n                    variants, p.(Tyr3933Cys) and an experimentally confirmed c.7715\u2009+\u20093A\u2009&gt;\u2009T consensus splice\u2010altering variant. In Family 3, the proband is compound heterozygous for a consensus donor splice site variant\n                    <jats:italic>LRP2<\/jats:italic>\n                    : c.8452_8452\u2009+\u20091del and p.(Cys3150Tyr). In mouse cochlea,\n                    <jats:italic>Lrp2<\/jats:italic>\n                    is expressed abundantly in the stria vascularis marginal cells demonstrated by smFISH, single\u2010cell and single\u2010nucleus RNAseq, suggesting that a deficiency of LRP2 may compromise the endocochlear potential, which is required for hearing.\n                    <jats:italic>LRP2<\/jats:italic>\n                    variants have been associated with Donnai\u2013Barrow syndrome and other multisystem pleiotropic phenotypes different from the phenotypes of the four cases reported herein. Our data expand the phenotypic spectrum associated with pathogenic variants in\n                    <jats:italic>LRP2<\/jats:italic>\n                    warranting their consideration in individuals with a combination of hereditary hearing loss and retinal dystrophy.\n                  <\/jats:p>","DOI":"10.1111\/cge.14312","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T00:45:16Z","timestamp":1676853916000},"page":"699-703","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Variants of\n                    <scp>\n                      <i>LRP2<\/i>\n                    <\/scp>\n                    , encoding a multifunctional cell\u2010surface endocytic receptor, associated with hearing loss and retinal dystrophy"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7788-8755","authenticated-orcid":false,"given":"Rabia","family":"Faridi","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Genetics National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH)  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2323-0004","authenticated-orcid":false,"given":"Rizwan","family":"Yousaf","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH)  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1041-3813","authenticated-orcid":false,"given":"Shoujun","family":"Gu","sequence":"additional","affiliation":[{"name":"Auditory Development and Restoration Program, NIDCD, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9064-0762","authenticated-orcid":false,"given":"Sayaka","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH)  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8065-7445","authenticated-orcid":false,"given":"Amy E.","family":"Turriff","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9884-3238","authenticated-orcid":false,"given":"Keith","family":"Pelstring","sequence":"additional","affiliation":[{"name":"Division of 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