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De novo mutation in KITLG gene causes a variant of Familial Progressive Hyper‐ and Hypo‐pigmentation (FPHH)
Author(s) -
Gorenjak Mario,
Fijačko Nino,
Bogomir Marko Pij,
Živanović Milanka,
Potočnik Uroš
Publication year - 2021
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1841
Subject(s) - genetics , exome sequencing , sanger sequencing , mutation , medicine , hypopigmentation , exon , phenotype , gene , biology
Familial Progressive Hyper‐ and Hypopigmentation is a pigmentary disorder characterized by a mix of hypo‐ and hyperpigmented lesions, café‐au‐lait spots and hypopigmented ash‐leaf macules. The disorder was previously linked to KITLG and various mutations have been reported to segregate in different families. Furthermore, association between KITLG mutations and malignancies was also suggested. Exome and SANGER sequencing were performed for identification of KITLG mutations. Functional in silico analyses were additionally performed to assess the findings. We identified a de novo mutation in exon 4 of KITLG gene causing NM_000899.4:c.[329A>T] (chr12:88912508A>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‐ and Hypopigmentation and malignancy due to its’ location on somatic cancer mutation locus. Additionally we also address difficulties with classification of the unique phenotype and propose a subtype within broader diagnosis.

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