{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:52:21Z","timestamp":1785491541566,"version":"3.56.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,3,15]],"date-time":"2017-03-15T00:00:00Z","timestamp":1489536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,7]]},"abstract":"We here report a family from Libya with three siblings suffering from early onset achalasia born to healthy parents. We analyzed roughly 5000 disease\u2010associated genes by a next\u2010generation sequencing (NGS) approach. In the analyzed sibling we identified two heterozygous variants in CRLF1<\/jats:styled-content><\/jats:italic> (cytokine receptor\u2010like factor 1). Mutations in CRLF1<\/jats:styled-content><\/jats:italic> have been associated with autosomal recessive Crisponi or cold\u2010induced sweating syndrome type 1 (CS<\/jats:styled-content>\/CISS1<\/jats:styled-content>), which among other symptoms also manifests with early onset feeding difficulties. Segregation analysis revealed compound heterozygosity for all affected siblings, while the unaffected mother carried the c.713dupC<\/jats:styled-content> (p.Pro239Alafs<\/jats:styled-content>*91) and the unaffected father carried the c.178T<\/jats:styled-content>>A (p.Cys60Ser<\/jats:styled-content>) variant. The c.713dupC<\/jats:styled-content> variant has already been reported in affected CS<\/jats:styled-content>\/CISS1<\/jats:styled-content> patients, the pathogenicity of the c.178T<\/jats:styled-content>>A variant was unclear. As reported previously for pathogenic CRLF1<\/jats:styled-content><\/jats:italic> variants, cytokine receptor\u2010like factor 1 protein secretion from cells transfected with the c.178T<\/jats:styled-content>>A variant was severely impaired. From these results we conclude that one should consider a CRLF1<\/jats:styled-content><\/jats:italic>\u2010related disorder in early onset achalasia even if other CS<\/jats:styled-content>\/CISS1<\/jats:styled-content> related symptoms are missing.<\/jats:p>","DOI":"10.1111\/cge.12953","type":"journal-article","created":{"date-parts":[[2016,12,17]],"date-time":"2016-12-17T08:10:05Z","timestamp":1481962205000},"page":"104-108","source":"Crossref","is-referenced-by-count":9,"title":["Mutations in CRLF1<\/scp><\/i> cause familial achalasia"],"prefix":"10.1111","volume":"92","author":[{"given":"A.","family":"Busch","sequence":"first","affiliation":[{"name":"Institute of Human Genetics Jena University Hospital Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"\u017darkovi\u0107","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Jena University Hospital Jena 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