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We herein report a 15\u2010month\u2010old male with peripheral lymphedema, facial dysmorphism, camptodactyly and generalized hypotonia. Solo exome sequencing revealed a homozygous splice site variant, c.12479+3A&gt;G in intron 14 of\n                    <jats:italic>FAT4<\/jats:italic>\n                    (NM_001291303.3). Reverse transcriptase\u2010PCR (RT\u2010PCR) was performed using cDNA isolated from patient\u2010derived fibroblasts, which revealed aberrant splicing. This study provides a report of an additional family with a novel biallelic splice site variant in\n                    <jats:italic>FAT4<\/jats:italic>\n                    which disrupts the normal splicing of the\n                    <jats:italic>FAT4<\/jats:italic>\n                    mRNA, leading to aberrant splicing causing a milder form of HKLLS2.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70166","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T05:59:12Z","timestamp":1776405552000},"page":"2019-2024","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biallelic Splicing Variant c.12479+\n                    <scp>3A<\/scp>\n                    &gt;G in\n                    <i>FAT4<\/i>\n                    Causes Hennekam Lymphangiectasia\u2010Lymphedema Syndrome 2"],"prefix":"10.1002","volume":"200","author":[{"given":"Selinda","family":"Mascarenhas","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashavi","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhil","family":"K. A.","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Pande","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huzail","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-8239","authenticated-orcid":false,"given":"Katta Mohan","family":"Girisha","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal, Manipal Academy of Higher Education  Manipal India"},{"name":"Department of Genetics College of Medicine &amp; Health Sciences, Sultan Qaboos University  Muscat Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7690-3201","authenticated-orcid":false,"given":"Periyasamy","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal, Manipal Academy of Higher Education  Manipal India"},{"name":"Medical Genetics, Institute of Medical Genetics and Pathology, University Hospital Basel  Basel Switzerland"},{"name":"Department of Biomedicine, University of Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju","family":"Shukla","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal, Manipal Academy of Higher Education  Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010014\u20101456\u2010y"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.484"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99027"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61392"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx297"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104427"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes15111363"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320340429"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38652"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24172"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63639"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2024.03.011"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201020584\u20104"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.179"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40633"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.07.001"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14040877"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70166","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70166","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70166","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:11:19Z","timestamp":1785834679000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":18,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/ajmg.a.70166"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70166","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]},"assertion":[{"value":"2025-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}