{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:17:36Z","timestamp":1790115456577,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gorlin syndrome can be caused by pathogenic\/likely pathogenic (P\/LP) variants in the tumor suppressor gene <jats:italic>PTCH1<\/jats:italic> (9q22.1\u2010q31), which encodes the receptor for the sonic hedgehog (SHH) ligand. We present a 12\u2010month\u2010old boy clinically diagnosed with Gorlin syndrome who was found to have significantly delayed development, palmar pitting, palmar and plantar keratosis, short hands, frontal bossing, coarse face, hypertelorism, a bifid rib, misaligned and missing teeth, and SHH\u2010activated medulloblastoma. Genetic testing, including a pediatric cancer panel and genome sequencing with peripheral blood, failed to identify any P\/LP variants in <jats:italic>PTCH1<\/jats:italic>. Paired tumor\/normal exome sequencing was performed, which identified a germline NM_000264.5 (<jats:italic>PTCH1<\/jats:italic>): c.361_362ins? alteration through manual review of sequencing reads. Clinical RNA sequencing further demonstrated an Alu insertion at this region (<jats:italic>PTCH1<\/jats:italic>: c.361_362insAlu), providing molecular confirmation of Gorlin syndrome. This finding exemplifies a unique mechanism for <jats:italic>PTCH1<\/jats:italic> disruption in the germline and highlights the importance of comprehensive analysis, including manual review of DNA sequencing reads and the utility of RNA analysis to detect variant types which may not be identified by routine genetic screening techniques.<\/jats:p>","DOI":"10.1002\/ajmg.a.63788","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T08:59:27Z","timestamp":1718182767000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Germline <scp><i>PTCH1<\/i><\/scp>: <scp>c.361_362insAlu<\/scp> alteration identified by comprehensive exome and <scp>RNA<\/scp> sequencing in a patient with <scp>Gorlin<\/scp> syndrome"],"prefix":"10.1002","volume":"194","author":[{"given":"Aaron Y.","family":"Mochizuki","sequence":"first","affiliation":[{"name":"Division of Oncology Cincinnati Children's Hospital Medical 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