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Sporadic occurrence of different forms of ichthyosis including IC have been previously reported in cattle. However, so far, no causative genetic variant has been found for bovine IC. Nine affected cattle presenting congenital xerosis, hyperkeratosis and scaling of the skin as well as urolithiasis and cystitis associated with retarded growth were examined. Skin histopathology revealed a severe, diffuse orthokeratotic hyperkeratosis with mild to moderate epidermal hyperplasia. The pedigree records indicated a monogenic recessive trait. Homozygosity mapping and whole-genome sequencing allowed the identification of a homozygous frameshift 1\u00a0bp insertion in the <jats:italic>FA2H<\/jats:italic> gene (c.9dupC; p.Ala4ArgfsTer142) located in a 1.92\u00a0Mb shared identical-by-descent region on chromosome 18 present in all cases, while the parents were heterozygous as expected for obligate carriers. These findings enable the selection against this sub-lethal allele showing an estimated frequency of ~\u20097.5% in Chianina top sires. A sporadic incidence of mild clinical signs in the skin of heterozygous carriers was observed. So far, pathogenic variants affecting the encoded fatty acid 2-hydroxylase catalyzing the synthesis of 2-hydroxysphingolipids have been associated with myelin disorders. In conclusion, this study represents the first report of an <jats:italic>FA2H<\/jats:italic>-related autosomal recessive inherited skin disorder in a mammalian species and adds <jats:italic>FA2H<\/jats:italic> to the list of candidate genes for ichthyosis in humans and animals. Furthermore, this study provides a DNA-based diagnostic test that enables selection against the identified pathogenic variant in the Chianina cattle population. However, functional studies are needed to better understand the expression of FA2H in IC-affected Chianina cattle.<\/jats:p>","DOI":"10.1007\/s00438-021-01824-8","type":"journal-article","created":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T16:03:30Z","timestamp":1633363410000},"page":"1313-1322","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A frameshift insertion in FA2H causes a recessively inherited form of ichthyosis congenita in Chianina cattle"],"prefix":"10.1007","volume":"296","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6438-7975","authenticated-orcid":false,"given":"Joana G. 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BMC Bioinform. https:\/\/doi.org\/10.1186\/1471-2105-13-134","DOI":"10.1186\/1471-2105-13-134"}],"container-title":["Molecular Genetics and Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00438-021-01824-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00438-021-01824-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00438-021-01824-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T11:56:24Z","timestamp":1635249384000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00438-021-01824-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,2]]},"references-count":47,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["1824"],"URL":"https:\/\/doi.org\/10.1007\/s00438-021-01824-8","relation":{},"ISSN":["1617-4615","1617-4623"],"issn-type":[{"value":"1617-4615","type":"print"},{"value":"1617-4623","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,2]]},"assertion":[{"value":"14 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study did not require official or institutional ethical approval as \u2018non-experimental clinical veterinary practices\u2019 are specifically excluded from being considered regulated procedures under The Animals (Scientific Procedures) Act (ASPA), 1986, Section 2(8) (). The cattle were handled according to good ethical standards and all live animals were blood sampled by a veterinary for diagnostic purposes on the farm to determine the cause of the disease. All other sampling was carried out postmortem on affected animals after euthanasia on humane grounds. The aim was to identify the cause of the congenital disorder and thereby improve the animal welfare situation on the Chianina cattle population by identifying the underlying genetic cause and preventing breeding of further cases.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}