{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:28:30Z","timestamp":1792787310183,"version":"4.5.0"},"reference-count":42,"publisher":"BMJ","issue":"10","funder":[{"name":"Pediatric Dermatology Research Alliance (PeDRA) and the National Eczema Association","award":["NEA23-CERG202"],"award-info":[{"award-number":["NEA23-CERG202"]}],"id":[{"id":"https:\/\/ror.org\/043ewr774","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2026,6,8]]},"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Bartter syndrome (BS) is a salt-losing renal tubulopathy classically characterised by hypokalaemic metabolic alkalosis and hyperreninaemic hyperaldosteronism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated the genetic cause of a Bartter-like phenotype in an adolescent patient with progressive nephrocalcinosis, hypercalciuria, polyuria, metabolic alkalosis, hypokalaemia, significantly elevated urine chloride, failure to thrive, and a salt-losing tubulopathy. Additionally, the patient presented with hypergammaglobulinaemia, abnormal cerebral white matter signal changes, skin autoinflammation, and mild intellectual disability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No pathogenic variants were detected in known BS-related genes, and all recessive BS genes were outside regions of homozygosity (ROH) in this patient from a consanguineous family. Instead, exome sequencing and homozygosity mapping identified a homozygous splicing variant, c.2702-2A&gt;G, in the epidermal growth factor receptor (\n                      <jats:italic>EGFR<\/jats:italic>\n                      ) gene within an ~28\u2009Mb ROH on chromosome 7p. RNA-Seq and RT-PCR analysis of the patient\u2019s RNA confirmed the pathogenicity of this variant, demonstrating aberrant splicing resulting in an in-frame retention of 27 nucleotides from intron 22 of\n                      <jats:italic>EGFR<\/jats:italic>\n                      . Immunofluorescence analysis of the proband\u2019s skin revealed a reduced\n                      <jats:italic>EGFR<\/jats:italic>\n                      protein level, rather than a complete absence, supporting a hypomorphic effect and likely explaining compatibility with survival into adolescence. Whereas previously reported\n                      <jats:italic>EGFR<\/jats:italic>\n                      variants have been associated with severe neonatal epithelial inflammation, bowel disease, and early mortality, our findings demonstrate that a hypomorphic variant can be compatible with survival into the second decade of life.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings support an association between a syndromic Bartter-like salt-losing tubulopathy with epithelial autoinflammation and a homozygous splice-altering\n                      <jats:italic>EGFR<\/jats:italic>\n                      pathogenic variant, thereby expanding the phenotypic spectrum of\n                      <jats:italic>EGFR<\/jats:italic>\n                      -associated disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2025-111461","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T18:59:17Z","timestamp":1782845957000},"page":"630-639","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Longest surviving patient with a homozygous splice-altering\n                    <i>EGFR<\/i>\n                    pathogenic variant presenting with skin autoinflammation and a Bartter-like salt-losing tubulopathy"],"prefix":"10.1136","volume":"63","author":[{"given":"Leila","family":"Youssefian","sequence":"first","affiliation":[{"name":"Center for Applied Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA"},{"name":"Department of Pathology, Cytogenetics Laboratory, City of Hope National Medical Center, Duarte, CA, 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