{"id":26993,"date":"2025-04-17T08:00:07","date_gmt":"2025-04-17T08:00:07","guid":{"rendered":"https:\/\/www.europesays.com\/uk\/26993\/"},"modified":"2025-04-17T08:00:07","modified_gmt":"2025-04-17T08:00:07","slug":"long-read-sequencing-pinpoints-genetic-basis-for-psychiatric-diagnosis-in-pediatric-case","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/uk\/26993\/","title":{"rendered":"Long-Read Sequencing Pinpoints Genetic Basis for Psychiatric Diagnosis in Pediatric Case"},"content":{"rendered":"

Researchers at Rady Children\u2019s Institute for Genomic Medicine (RCIGM) in San Diego have successfully applied long-read genome sequencing to reveal the genetic underpinnings of complex psychiatric conditions in a 17-year-old patient, showcasing the potential of this advanced technology for clinical diagnosis and future gene therapies.<\/p>\n

In the recent study, \u201cLong-Read Genome Sequencing in Clinical Psychiatry: RFX3 Haploinsufficiency in a Hospitalized Adolescent With Autism, Intellectual Disability, and Behavioral Decompensation<\/a>,\u201d published in the American Journal of Psychiatry, researchers utilized the PacBio Revio platform, a long-read sequencing technology, to pinpoint the diagnosis of RFX3\u202fhaploinsufficiency syndrome in an adolescent with autism spectrum disorder and intellectual disability.<\/p>\n

While testing children for genetic disorders, a percentage of young patients are found to have variants of uncertain significance that short-read sequencing is unable to decipher. That\u2019s where long-read sequencing can shed some light. RCIGM clinicians have used this technology to understand and diagnose pediatric patients. Stephen Kingsmore, PhD, the RCIGM president and CEO, is well known in the genomics field for leading long-read studies<\/a> on rare disease diagnostics.<\/p>\n

\"AaronAaron D. Besterman, MD
Rady Children\u2019s Institute for Genomic Medicine<\/p>\n

Aaron D. Besterman, MD, a child psychiatrist and genetics researcher at RCIGM who co-authored the new study, told GEN that this was part of a larger project that primarily used short-read sequencing to study children with neurodevelopmental disorders. \u201cThe goal of this study was really to better characterize and understand who these kids are exactly,\u201d Besterman said. Reaching a confirmed diagnosis can be a big step to improving the outcomes for these young patients.<\/p>\n

A tale of two platforms<\/strong><\/p>\n

Investigators must face several considerations when choosing between long-read platforms for clinical diagnostics, particularly when cataloging complex structural variants.<\/p>\n

\"FromJonathan Sebat, PhD
Director of the Verge Center
University of California, San Diego<\/p>\n

Jonathan Sebat, PhD, director of the Verge Center at the University of California, San Diego, and a co-author of the study, told GEN that the team selected PacBio over the other major long-read sequencing platform, produced by the U.K.\u2019s Oxford Nanopore (ONT). After weighing the pros and cons of both platforms, the team decided to use PacBio to maximize accuracy, Sebat said.<\/p>\n

\u201cBoth technologies are progressing rapidly. They are quite complementary and are often used in combination,\u201d Sebat said. \u201cHistorically, PacBio has had an advantage in terms of the accuracy of the sequencing reads. ONT has the ability to generate much longer reads, which is very\u202fuseful for assembling the reads into a complete genome.\u201d<\/p>\n

\u201cONT has also made improvements to its sequencing accuracy so both platforms are strong contenders for eventually becoming a first-line comprehensive genetic test.\u201d<\/p>\n

Through PacBio sequencing, the San Diego team uncovered a complex arrangement with both deletions and duplications in the RFX3 gene, ultimately leading to a loss of function. This allowed them to categorize the variant and make a more certain and accurate diagnosis in the teenage patient.<\/p>\n

The long view: Sequencing toward the future<\/strong><\/p>\n

The successful diagnosis provided significant relief for the patient\u2019s family, delivering answers after years of uncertainty. Beyond personal closure, genetic insights from long-read sequencing also open avenues for community support, reproductive counseling, gene therapy, and tailored medical management strategies.<\/p>\n

\u201cThe last important piece of this is medical management,\u201d Besterman added. Through long-read sequencing, Besterman believes that a few cases in the study have the potential to uncover genes associated with autism and other medical conditions, which could prevent other patients from a diagnostic odyssey.<\/p>\n

\"\"Credit: Kateryna Kon\/Science Photo Library\/Getty Images<\/p>\n

Despite its promising outcomes, the broader clinical adoption of long-read sequencing faces several barriers. The relatively high cost, limited accessibility, and the need for extensive medical genetics training among clinicians are currently holding back widespread use.<\/p>\n

\u201cI think it\u2019s important that the general psychiatry field start to become more familiar with this technology because it will become more and more common and can play a very important role in making diagnoses that are not possible through any other means,\u201d stated Besterman.<\/p>\n

Looking ahead, the researchers emphasize the importance of integrating long-read sequencing into broader diagnostic pipelines, not as a replacement for short-read methods but as a powerful complement for cases where other tools fall short.<\/p>\n

\u201cLong-read sequencing is certainly the type of diagnostic technology that\u2019s going to play a huge role in precision medicine moving forward. I think there will also be a lot of integration with other omics platforms and technology,\u201d said Besterman. Instead of solely focusing on genetics, the integration of transcriptomics and proteomics, among others, with clinical data to inform diagnoses, should be considered.<\/p>\n

As clinical implementation grows, the case from RCIGM underscores the importance of continued investment and innovation in genomic technologies, highlighting a hopeful path forward for complex psychiatric conditions previously considered diagnostically elusive.<\/p>\n","protected":false},"excerpt":{"rendered":"Researchers at Rady Children\u2019s Institute for Genomic Medicine (RCIGM) in San Diego have successfully applied long-read genome sequencing…\n","protected":false},"author":2,"featured_media":26994,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3846],"tags":[7371,16412,267,12212,16413,16414,11925,12,16411,6380,3913,70,11920,16415,16,15],"class_list":{"0":"post-26993","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-diagnosis","9":"tag-gene-therapy-therapeutics","10":"tag-genetics","11":"tag-genome-sequencing","12":"tag-genomic-medicine","13":"tag-long-read-sequencing","14":"tag-neurodevelopmental-disorder","15":"tag-news","16":"tag-omics","17":"tag-pediatrics","18":"tag-psychiatry","19":"tag-science","20":"tag-topics","21":"tag-treatment-outcome","22":"tag-uk","23":"tag-united-kingdom"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@uk\/114352254408568842","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/26993","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/comments?post=26993"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/26993\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media\/26994"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media?parent=26993"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/categories?post=26993"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/tags?post=26993"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}