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Mendeliome v1.3453 KCTD15 Achchuthan Shanmugasundram gene: KCTD15 was added
gene: KCTD15 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: KCTD15 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCTD15 were set to 38296633
Phenotypes for gene: KCTD15 were set to frontonasal dysplasia, MONDO:0016643
Mode of pathogenicity for gene: KCTD15 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: KCTD15 was set to AMBER
Added comment: PMID:38296633 (2024) reported a two-generation family affected by a distinctive phenotype comprising a lipomatous frontonasal malformation, anosmia, cutis aplasia of the scalp and/or sparse hair, and congenital heart disease. A heterozygous c.310G>C variant encoding p.(Asp104His) within the BTB domain of KCTD15 was identified in the affected father and daughter via exome sequencing and the variant segregated with the phenotype. A de novo heterozygous c.263G>A variant encoding p.(Gly88Asp) was identified via targeted DNA sequencing in a similarly affected sporadic patient.

There is some functional evidence available from structural analyses, which demonstrated that missense substitutions act through a dominant negative mechanism by disrupting the higher order structure of the KCTD15 protein complex.
Sources: Literature