mutation<\/a> in the SYNGAP1 gene.<\/p>\nThe first key finding of the study is that there is considerable clinical variability among patients, even when they share mutations in the same gene.”<\/p>\n
Professor Bru Cormand, head of the UB’s Neurogenetics Research Group and an ICREA Academia 2021 researcher<\/p>\n
“Secondly – he continues – a link has been discovered between genetic characteristics and symptoms, although it is neither direct nor straightforward.”<\/p>\n
Another significant finding suggests that the severity of the disease does not depend solely on mutations in the SYNGAP1 gene, “but also on other genetic factors that may influence its clinical presentation,” notes Marina Mitjans, a researcher with the Ram\u00f3n y Cajal programme at the UB’s Department of Genetics, Microbiology and Statistics.<\/p>\n
The study has also identified four new variants of the SYNGAP1 gene, “which are likely to be pathogenic and had not been described previously; specifically, the variants p.Ala591Pro, p.Val447Leufs*5, p.Thr674Profs*36 and p.Arg143Glnfs*9”, notes Professor Ferran Casals, from the same department at the UB. He also adds that “in cases where we could analyse the parents’ DNA, we could confirm that these variants have arisen de novo; in other words, they are new mutations that have not been inherited from the parents.”<\/p>\n
Can mutations in the gene predict disease severity?<\/p>\n
One of the key questions raised by the study was whether the type of genetic variant can predict the severity of the disease.<\/p>\n
Although this association is only partial, some significant patterns have been identified. “For example, we know that the location of the variant within the gene is an important factor. More specifically, variants located in the PH domain of the gene are associated with a milder phenotype, with less impairment of language, fewer cases of epilepsy and lower overall severity,” says Bru Cormand.<\/p>\n
“For this reason, we suggest that a correlation between genotype and phenotype does exist in this encephalopathy, but it is complex. It is not just a question of which variant is present, but also where it is located and the patient’s overall genetic context,” adds Cormand.<\/p>\n
Another significant finding is that patients with the same SYNGAP1 mutation can show markedly different clinical manifestations. “This finding suggests that the severity of the disease does not depend solely on the specific SYNGAP1 mutation, but probably also on other genetic modifier factors,” say Mitjans and Casals.<\/p>\n
It is also worth noting that two-thirds of patients affected by this encephalopathy have also been diagnosed with autism. “For this reason, we are talking about one of the monogenic forms of autism spectrum disorder, which is usually of polygenic origin,” the team points out.<\/p>\n
To obtain these results, the team analysed whole-genome sequencing data covering all the exons in many of the patients – that is, around 200,000 segments comprising some 40 million nucleotides.<\/p>\n
“These sequences have enabled the detection, in addition to the alteration in the SYNGAP1 gene, of other mutations in genes whose products interact with the SYNGAP1 protein, such as SHANK1, SHANK3 and NLGN2, among others. In general, patients with rare mutations in these genes appear to have a more severe form of the disease”, the researchers conclude. <\/p>\n
Source:<\/p>\n
Journal reference:<\/p>\n
Aranda, S., et al. (2026). Genotype-phenotype correlations and putative modifier genes in SYNGAP1 Encephalopathy.\u00a0Neurobiology of Disease. DOI: 10.1016\/j.nbd.2026.107357.\u00a0https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0969996126001026<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"SYNGAP1 encephalopathy is a rare genetic disorder for which there is no treatment, causing epilepsy, intellectual disability, psychomotor…\n","protected":false},"author":2,"featured_media":800,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[486,164,3393,5295,19187,5352,3718,1356,8283,163,85,46,10689,9436,5198,1360],"class_list":{"0":"post-405137","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-autism","9":"tag-brain","10":"tag-disability","11":"tag-encephalopathy","12":"tag-epilepsy","13":"tag-gene","14":"tag-genes","15":"tag-genetic","16":"tag-genetic-disorder","17":"tag-health","18":"tag-il","19":"tag-israel","20":"tag-mutation","21":"tag-phenotype","22":"tag-protein","23":"tag-research"},"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/405137","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/comments?post=405137"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/405137\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media\/800"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media?parent=405137"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/categories?post=405137"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/tags?post=405137"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}