Juan J. Alban1, Alejandra Arango-Ramirez1, Jorge A. Olave-Rodriguez2, Jose A. Nastasi-Catanese2,3 and Lisa X. Rodriguez2,3 1Fundación Valle del Lili, Center of Clinical Research, Cali, 760026, Colombia; 2Faculty of Health Sciences, Icesi University, Cali, 760031, Colombia; 3Fundación Valle del Lili, Department of Human Genetics, Cali, 760026, Colombia Corresponding author: lisa.rodriguezfvl.org.co

Here, we highlight the case of a 31-yr-old man who had clinical features of primary hypertrophic osteoarthropathy (PHOAR) and harbored a homozygous variant (c.38C > A, p.Ala13Glu) in the HPGD gene, as indicated by whole-exome sequencing (WES). This variant has been previously classified by our laboratory as a variant of uncertain significance (VUS). However, another patient with the same phenotype and the same homozygous variant in HPGD was subsequently reported. In reassessing the variant, the absence of this variant in the gnomAD population database, supporting computational predictions, observation in homozygosity in two probands, and specificity of the phenotype for HPGD, all provide sufficient evidence to reclassify the HPGD c.38C > A, p.Ala13Glu variant as likely pathogenic.

Received April 27, 2023. Accepted August 8, 2023.

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