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This summary reviews the available evidence regarding the association between FABP12 (HGNC:34524) and familial multiple trichoepithelioma (MONDO_0011114), a condition typically inherited in an autosomal dominant manner. The disorder is characterized by multiple benign skin tumors, and its genetic basis has been predominantly linked to other genes in previous studies. In the case under review, the evidence stems from a five‐generation Han Chinese family in which patients exhibited both Marie Unna hereditary hypotrichosis and multiple familial trichoepithelioma (PMID:30809827).
Genetic assessment of this family identified a FABP12 variant (rs536105592 G>A) in patients with multiple familial trichoepithelioma. However, the mutation did not conform to the standardized HGVS nomenclature for coding changes (i.e. a variant beginning with “c.” and including an amino‑acid change), and no robust segregation data or additional independent case reports were provided. Hence, the current genetic evidence for a pathogenic role of FABP12 in familial multiple trichoepithelioma remains inconclusive (PMID:30809827).
The reported evidence lacks critical details such as a properly formatted variant description and supportive segregation analysis in additional affected relatives. Although thirteen family members were examined using Sanger sequencing, the FABP12 variant appears to be an incidental finding, with no further validation through either further genetic screening or recurrent observation in unrelated probands (PMID:30809827).
There is also a notable absence of targeted functional or experimental studies that assess the biological impact of the FABP12 variant. No in vitro or in vivo assays have been reported to demonstrate a deleterious effect on protein function or a mechanistic link to the pathogenesis of familial multiple trichoepithelioma. This lack of functional data significantly limits the overall support for a causative role of FABP12.
In addition, the evidence is confounded by the concurrent identification of a pathogenic HR mutation that clearly accounts for the Marie Unna hereditary hypotrichosis phenotype. The co‐occurrence of the FABP12 variant alongside a well‐established causative mutation further calls into question the relevance of the FABP12 finding with respect to familial multiple trichoepithelioma. As such, the data do not conclusively support an independent role for FABP12 in disease pathogenesis.
In conclusion, while the FABP12 variant was detected in affected individuals of a single large family, the quality and extent of the evidence do not meet the criteria for a robust gene–disease association. The overall evidence for FABP12 in familial multiple trichoepithelioma is thus classified as Limited. Key take‑home: the incidental nature of the FABP12 variant diminishes its clinical utility for diagnostic decision‑making and warrants further investigation before it can be considered for commercial or publication use.
Gene–Disease AssociationLimitedA single family study identified a FABP12 variant incidentally in patients, lacking proper HGVS formatting, robust segregation, or independent replication (PMID:30809827). Genetic EvidenceLimitedThe available genetic evidence is limited to an incidental variant without a valid coding description or supporting segregation data, reducing its contribution to the gene–disease association. Functional EvidenceLimitedNo functional assays or experimental studies have been performed to validate a pathogenic role of FABP12 in familial multiple trichoepithelioma. |