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The disorder was previously linked to <jats:italic>KITLG<\/jats:italic> and various mutations have been reported to segregate in different families. Furthermore, association between <jats:italic>KITLG<\/jats:italic> mutations and malignancies was also suggested. Exome and SANGER sequencing were performed for identification of <jats:italic>KITLG<\/jats:italic> mutations. Functional in silico analyses were additionally performed to assess the findings. We identified a de novo mutation in exon 4 of <jats:italic>KITLG<\/jats:italic> gene causing NM_000899.4:c.[329A&gt;T] (chr12:88912508A&gt;T) leading to NP_000890.1:p.(Asp110Val) substitution in the 3rd alpha helix. It was predicted as pathogenic, located in a conserved region and causing an increase in hydrophobicity in the KITLG protein. Our findings clearly confirm an additional hot spot of KITLG mutations in the 3rd alpha helix, which very likely increases the risk of malignancies. To our knowledge the present study provides the strongest evidence of association of the KITLG mutation with both Familial Progressive Hyper\u2010 and Hypopigmentation and malignancy due to its\u2019 location on somatic cancer mutation locus. Additionally we also address difficulties with classification of the unique phenotype and propose a subtype within broader diagnosis.<\/jats:p>","DOI":"10.1002\/mgg3.1841","type":"journal-article","created":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T08:46:32Z","timestamp":1635583592000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<i>De novo<\/i> mutation in <i>KITLG<\/i> gene causes a variant of Familial Progressive Hyper\u2010 and Hypo\u2010pigmentation (FPHH)"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4208-9683","authenticated-orcid":false,"given":"Mario","family":"Gorenjak","sequence":"first","affiliation":[{"name":"Faculty of Medicine Centre for Human Molecular Genetics and Pharmacogenomics University of Maribor Maribor Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nino","family":"Fija\u010dko","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences Department of Nursing Maribor Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pij","family":"Bogomir Marko","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereal Diseases University Clinical Centre Maribor Maribor Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milanka","family":"\u017divanovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Institute of Pathology University of Ljubljana Ljubljana Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uro\u0161","family":"Poto\u010dnik","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Centre for Human Molecular Genetics and Pharmacogenomics University of Maribor Maribor Slovenia"},{"name":"Faculty of Chemistry and Chemical Engineering Laboratory of Biochemistry, Molecular Biology and Genomics University of Maribor Maribor Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,10,30]]},"reference":[{"issue":"7","key":"e_1_2_9_2_1","first-page":"20","article-title":"Predicting functional effect of human missense mutations using PolyPhen\u20102","volume":"7","author":"Adzhubei I.","year":"2013","journal-title":"Current Protocols in Human Genetics"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.29"},{"key":"e_1_2_9_5_1","unstructured":"Andrews S.(2010).FastQC: A quality control tool for high throughput sequence data. 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