{"id":256,"date":"2023-12-30T16:58:06","date_gmt":"2023-12-30T16:58:06","guid":{"rendered":"http:\/\/sebgc.es\/blog\/?guid=4e6d2cc21aeea473b2cb9e32e3540225"},"modified":"2023-12-30T16:58:06","modified_gmt":"2023-12-30T16:58:06","slug":"intermediate-effect-size-p-arg637gln-in-fhod3-increases-risk-of-hcm-and-is-associated-with-an-aggressive-phenotype-in-homozygous-carriers","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2023\/12\/30\/intermediate-effect-size-p-arg637gln-in-fhod3-increases-risk-of-hcm-and-is-associated-with-an-aggressive-phenotype-in-homozygous-carriers\/","title":{"rendered":"Intermediate-effect size p.Arg637Gln in FHOD3 increases risk of HCM and is associated with an aggressive phenotype in homozygous carriers"},"content":{"rendered":"<p>Formin homology 2 domain-containing 3 (<I>FHOD3<\/I>) gene has emerged as one of the main non-sarcomeric genes associated with hypertrophic cardiomyopathy (HCM), but no cases of biallelic variants associated with disease have been described to date. From 2014 until 2021, <I>FHOD3<\/I> was evaluated in our center by next-generation sequencing in 22 806 consecutive unrelated probands. The p.Arg637Gln variant in <I>FHOD3<\/I> was enriched in our HCM cohort (284 of 9668 probands; 2.94%) compared with internal controls (64 of 11 480; 0.59%) and gnomAD controls (373 of 64 409; 0.58%), with ORs of 5.40 (95% CI: 4.11 to 7.09) and 5.19 (95% CI: 4.44 to 6.07). The variant affects a highly conserved residue localised in a supercoiled alpha helix considered a clustering site for HCM variants, and in heterozygosis can act as a predisposing factor (intermediate-effect variant) for HCM, with an estimated penetrance of around 1%. Additionally, seven homozygous carriers of p.Arg637Gln in <I>FHOD3<\/I> were identified. All but one (unaffected) showed an early presentation and a severe HCM phenotype. All this information suggest that p.Arg637Gln variant in <I>FHOD3<\/I> is a low-penetrant variant, with an intermediate effect, that contributes to the development of HCM in simple heterozygosis, being associated with a more severe phenotype in homozygous carriers.<\/p>","protected":false},"excerpt":{"rendered":"<p>Formin homology 2 domain-containing 3 (FHOD3) gene has emerged as one of the main non-sarcomeric genes associated with hypertrophic cardiomyopathy (HCM), but no cases of biallelic variants associated with disease have been described to date. From 2014 &#8230;<\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,8],"tags":[],"class_list":["post-256","post","type-post","status-publish","format-standard","hentry","category-articulos","category-jmg-first"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/256","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=256"}],"version-history":[{"count":1,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/256\/revisions"}],"predecessor-version":[{"id":257,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/256\/revisions\/257"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=256"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=256"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=256"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}