| Texto completo | |
| Autor(es): |
Arcanjo, Adriano Miguel
;
de Souza, Amanda Fernandes
;
Quedas, Elisangela Pereira de Souza
;
Correia-Deur, Joya Emilie de Menezes
;
Ferreira, Dalton Libanio
;
Toledo, Sergio Pereira de Almeida
;
Lourenco Jr, Delmar Muniz
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JBMR PLUS; v. 9, n. 4, p. 15-pg., 2025-04-01. |
| Resumo | |
Primary hypertrophic osteoarthropathy (PHO) is a rare autosomal recessive disease caused by pathogenic variants (PVs) in HPGD and SLCO2A1 genes whose phenotypes are, respectively, designated as PHOAR1 and PHOAR2. Recently, a dominant inherited form (PHOAD) was identified in SLCO2A1 heterozygotes whose PHO penetrance is widely unknown, and data on phenotype are markedly limited. Our aim was to reveal the penetrance and extend/refine data on phenotype of SLCO2A1 heterozygotes. Both genes were sequenced using Sanger sequencing. The 4 probands had a typical complete form (CF) of PHO. Mean ages at symptom onset and clinical diagnosis were, respectively, 18.5 +/- 2.7 (16-22) years and 22 +/- 3.4 (18-26) years. They were homozygotes for SLCO2A1 (p.Q188R, p.C420F, p.A176T; p.G104*) PVs; 2 were novel variants. We focused on 14 SLCO2A1 heterozygous screened relatives from 3 families: 5 elderly individuals (mean age: 78 +/- 6.7 [72-86] years) of the parental generation were affected, 2 by incomplete form (IF) and 3 with isolated digital clubbing (IDC). Combining our 14 carriers and 33 reported so far, the estimated overall PHO penetrance was 70%, being significantly higher in men (83% vs 50%; p = .024) and individuals carrying truncated SLCO2A1 PVs (88% vs 53%; p = .053). In turn, the periostosis penetrance rate in women was 28% (5/18), including our oldest patient (86 years). In the probands, the predominant phenotypes were CF (64%) and IF (36%). Among screened carriers, phenotypes were IDC (41%) followed by IF and fruste form (FF) (28%, each), whereas IDC and FF were the predominant phenotypes in screened men and women, respectively. As a novelty, we uncovered an incomplete penetrance of PHO in SLCO2A1 heterozygotes, with higher rates in elderly individuals, males, and those with truncated PVs. Regarding phenotype, PHO is more pronounced in males, periostosis is likely more frequent in females than previously documented in PHOAR2, and IDC may represent a distinct clinical feature in SLCO2A1 heterozygotes. Primary hypertrophic osteoarthropathy (PHO) is a rare genetic disorder affecting bones and skin. It causes bone growth around the edges of bones, thickened skin, widening of fingers and toes, and wrinkling on the scalp. PHO has 2 forms: the recessive form (PHOAR1 and PHOAR2), which occurs when both parents pass on faulty genes, and the dominant form (PHOAD), where only 1 parent passes on the faulty gene. Our study found that PHO in the dominant form does not appear in all carriers, but is more common in older individuals, men, and those with specific genetic changes. (AU) | |
| Processo FAPESP: | 16/07504-2 - Avaliação de painéis gênicos baseados em sequenciamento de nova geração aplicados ao diagnóstico diferencial de neoplasia endócrina tipo 1 e na análise de correlações genótipo-fenótipo. |
| Beneficiário: | Delmar Muniz Lourenço Jr |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |