Periodical
Familial multiple discoid fibromas is linked to a locus on chromosome 5 including the FNIP1gene
| العنوان: | Familial multiple discoid fibromas is linked to a locus on chromosome 5 including the FNIP1gene |
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| المؤلفون: | van de Beek, Irma, Glykofridis, Iris E., Tanck, Michael W. T., Luijten, Monique N. H., Starink, Theo M., Balk, Jesper A., Johannesma, Paul C., Hennekam, Eric, van den Hoff, Maurice J. B., Gunst, Quinn D., Gille, Johan J. P., Polstra, Abeltje M., Postmus, Pieter E., van Steensel, Maurice A. M., Postma, Alex V., Wolthuis, Rob M. F., Menko, Fred H., Houweling, Arjan C., Waisfisz, Quinten |
| المصدر: | Journal of Human Genetics; April 2023, Vol. 68 Issue: 4 p273-279, 7p |
| مستخلص: | Previously, we reported a series of families presenting with trichodiscomas, inherited in an autosomal dominant pattern. The phenotype was named familial multiple discoid fibromas (FMDF). The genetic cause of FMDF remained unknown so far. Trichodiscomas are skin lesions previously reported to be part of the same spectrum as the fibrofolliculoma observed in Birt-Hogg-Dubé syndrome (BHD), an inherited disease caused by pathogenic variants in the FLCNgene. Given the clinical and histological differences with BHD and the exclusion of linkage with the FLCNlocus, the phenotype was concluded to be distinct from BHD. We performed extensive clinical evaluations and genetic testing in ten families with FMDF. We identified a FNIP1frameshift variant in nine families and genealogical studies showed common ancestry for eight families. Using whole exome sequencing, we identified six additional rare variants in the haplotype surrounding FNIP1, including a missense variant in the PDGFRBgene that was found to be present in all tested patients with FMDF. Genome-wide linkage analysis showed that the locus on chromosome 5 including FNIP1was the only region reaching the maximal possible LOD score. We concluded that FMDF is linked to a haplotype on chromosome 5. Additional evaluations in families with FMDF are required to unravel the exact genetic cause underlying the phenotype. When evaluating patients with multiple trichodisomas without a pathogenic variant in the FLCNgene, further genetic testing is warranted and can include analysis of the haplotype on chromosome 5. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 14345161 1435232X |
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| DOI: | 10.1038/s10038-022-01113-1 |