American Journal of Medical Genetics Part B: Neuropsychiatric Genetics最新文献

{"title":"Cover Image, Volume 198, Number 7, October 2025","authors":"Clio E. Franklin,&nbsp;Murat Altinay,&nbsp;Kala Bailey,&nbsp;Mahendra T. Bhati,&nbsp;Brent R. Carr,&nbsp;Susan K. Conroy,&nbsp;Khurshid Khurshid,&nbsp;William M. McDonald,&nbsp;Brian J. Mickey,&nbsp;James W. Murrough,&nbsp;Sean M. Nestor,&nbsp;Thomas Nickl-Jockschat,&nbsp;Irving M. Reti,&nbsp;Gerard Sanacora,&nbsp;Nicholas T. Trapp,&nbsp;Biju Viswanath,&nbsp;Jesse H. Wright,&nbsp;Peter P. Zandi,&nbsp;James B. Potash","doi":"10.1002/ajmg.b.33059","DOIUrl":"https://doi.org/10.1002/ajmg.b.33059","url":null,"abstract":"<p>The cover image is based on the article <i>Genetics of Response to ECT, TMS, Ketamine and Esketamine</i> by Clio E. Franklin et al., https://doi.org/10.1002/ajmg.b.33038.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"198 7","pages":""},"PeriodicalIF":1.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.33059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review of the Application of Graph Neural Networks to Extract Candidate Genes and Biological Associations.","authors":"Ankita Saxena, Bridgette Nixon, Amelia Boyd, James Evans, Stephen V Faraone","doi":"10.1002/ajmg.b.33031","DOIUrl":"10.1002/ajmg.b.33031","url":null,"abstract":"<p><p>The development of high throughput technologies has resulted in the collection of large quantities of genomic and transcriptomic data. However, identifying disease-associated genes or networks from these data has remained an ongoing challenge. In recent years, graph neural networks (GNNs) have emerged as a promising analytical tool, but it is not well understood which characteristics of these models result in improved performance. We conducted a systematic search and review of publications that used GNNs to identify disease-associated biological interactions. Information was extracted about model characteristics and performance with the goal of examining the relationship between these factors and performance. Data leakage was found in 31% of these models. For node level tasks, univariate positive associations were identified between model accuracy and use of hyper parameter optimization, data leakage via hyperparameter optimization, test set size, and total dataset size. Among graph level tasks, an increase in AUC was identified in association with testing method and a decrease with optimization reporting. Data leakage may pose an issue for GNN-based approaches; the adoption of best practice guidelines and consistent reporting of model design would be beneficial for future studies.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"3-18"},"PeriodicalIF":1.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Transcriptome-Wide Mendelian Randomization Study in Isolated Human Immune Cells Highlights Risk Genes Involved in Viral Infections and Potential Drug Repurposing Opportunities for Schizophrenia.","authors":"David Stacey, Liam Gaziano, Preethi Eldi, Catherine Toben, Beben Benyamin, S Hong Lee, Elina Hyppönen","doi":"10.1002/ajmg.b.33028","DOIUrl":"10.1002/ajmg.b.33028","url":null,"abstract":"<p><p>Schizophrenia is a neurodevelopmental psychiatric disorder characterized by symptoms of psychosis, thought disorder, and flattened affect. Immune mechanisms are associated with schizophrenia, though the precise nature of this relationship (causal, correlated, consequential) and the mechanisms involved are not fully understood. To elucidate these mechanisms, we conducted a transcriptome-wide Mendelian randomization study using gene expression exposures from 29 human cis-eQTL data sets encompassing 11 unique immune cell types, available from the eQTL catalog. These analyses highlighted 196 genes, including 67 located within the human leukocyte antigen (HLA) region. Enrichment analyses indicated an overrepresentation of immune genes, which was driven by the HLA genes. Stringent validation and replication steps retained 61 candidate genes, 27 of which were the sole causal signals at their respective loci, thereby representing strong candidate effector genes at known risk loci. We highlighted L3HYPDH as a potential novel schizophrenia risk gene and DPYD and MAPK3 as candidate drug repurposing targets. Furthermore, we performed follow-up analyses focused on one of the candidate effectors, interferon regulatory transcription factor 3 (IRF3), which coordinates interferon responses to viral infections. We found evidence of shared genetic etiology between schizophrenia and autoimmune diseases at the IRF3 locus, and a significant enrichment of IRF3 chromatin binding at known schizophrenia risk loci. Our findings highlight a novel schizophrenia risk gene, potential drug repurposing opportunities, and provide support for IRF3 as a schizophrenia hub gene, which may play critical roles in mediating schizophrenia-autoimmune comorbidities and the impact of infections on schizophrenia risk.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"19-31"},"PeriodicalIF":1.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do Influential Articles on the Genetics of Autism Show Evidence of Engagement With the Autistic Community?","authors":"Heidi Kristiina Kaljusto, Emma Wilson, Sue Fletcher-Watson","doi":"10.1002/ajmg.b.33030","DOIUrl":"10.1002/ajmg.b.33030","url":null,"abstract":"<p><p>Investigations into the etiology and genetic basis of autism continue to drive much autism research, yet reports are emerging of this research not aligning with priorities of autistic people. Engagement of autistic people in the research process is a key way to take their perspectives on board. We investigated whether influential genetic autism research shows evidence of engagement with the autistic community via indicators in published article texts. Through text mining of the abstracts of articles mentioning the words \"autism\" or \"autistic,\" we found minimal prevalence of progressive terminology associated with autism. We also devised a novel rating system to assess three hallmarks of autistic community engagement: presence of non-stigmatizing language, referencing community priorities, and the use of participatory methods. We reviewed 149 articles within leading autism and genetic journals. Minimal evidence of engagement with the autistic community was found within all three hallmarks. Genetics researchers focused on autism should embrace opportunities to engage with the autistic community to bring their work into closer alignment with their priorities, yielding scientific and moral benefits.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"46-61"},"PeriodicalIF":1.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic Manifestations of a New Variant in HDAC4 Gene.","authors":"Monica Ianniello, Valentina De Angelis, Alessandro Ottaiano, Raffaella Ruggiero, Roberto Sirica, Nadia Petrillo, Antonio Fico, Tania Cerbone, Cecilia Rosania, Raffaella Mormile, Carmine Picone, Mariachiara Santorsola, Giovanni Savarese","doi":"10.1002/ajmg.b.33029","DOIUrl":"10.1002/ajmg.b.33029","url":null,"abstract":"<p><p>Psychomotor development delays affect 1%-3% of children and encompass a wide range of motor, cognitive, and social impairments. The histone deacetylase 4 (HDAC4) gene, critical for neurodevelopmental pathways, has been associated with developmental delays, autism spectrum disorders, and cognitive impairments. Here, we report a case of a female patient with global psychomotor developmental delay, hypotonia, and feeding difficulties since infancy. By the age of seven, she developed epilepsy, later diagnosed as Lennox-Gastaut syndrome. Brain magnetic resonance imaging revealed reduced white matter and polymicrogyria-like cortical malformations, primarily in the fronto-basal regions. Whole-exome sequencing identified a novel de novo HDAC4 mutation (p.Gln1046AspfsTer29; c.3136_3137delCA), resulting in a frameshift and a premature stop codon. Additional phenotypic features included distinct craniofacial abnormalities and hypertrichosis. This report highlights the critical role of HDAC4 in psychomotor development and cognitive function, expands the phenotypic spectrum associated with HDAC4 mutations, and suggests a potential link to epilepsy and cortical malformations.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"32-37"},"PeriodicalIF":1.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC00665/miR-132-5p Reduces Inflammation in Epileptic Cells by Targeting MAPK3.","authors":"Qi-Ming Pang, Cui Wang, Bang-Tao Li, Su-Li Zhang, Jiao-Yang Li, Shuo Gu","doi":"10.1002/ajmg.b.33027","DOIUrl":"10.1002/ajmg.b.33027","url":null,"abstract":"<p><p>To investigate the role of miR-132-5p in the inflammatory response in epilepsy. Peripheral blood was collected from epileptic and healthy children, and the expression of LINC00665 and miR-132-5p was detected by q-PCR. Epilepsy cell models were constructed with microglia, transfected with miR-132-5p inhibitor and NC, and the expression of LINC00665 and miR-132-5p was detected by q-PCR, the expression of TNF-α, IL-1β, and IL-6 in the cell supernatant was detected by ELISA, and the protein levels of NLRP3 and MAPK3 were detected by WB. Finally, the targeting relationship between LINC00665 and miR-132-5p was verified by dual luciferase assay. The expression levels of both LINC00665 and miR-132-5p in the peripheral blood of children with epilepsy were significantly higher than those of healthy children. After transfection of epileptic cells with miR-132-5p inhibitor, the expression levels of LINC00665 and miR-132-5p were increased, and the expression levels of TNF-α, IL-1β, IL-6, NLRP3, and MAPK3 were decreased. Dual luciferase assay showed targeted binding of LINC00665 and miR-132-5p. LINC00665/miR-132-5p attenuates inflammatory responses in epileptic cells by targeting MAPK3.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"38-45"},"PeriodicalIF":1.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Randomized Double-Blind Placebo-Controlled Trial of Guanfacine Extended Release for Aggression and Self-Injurious Behavior Associated With Prader-Willi Syndrome.","authors":"Deepan Singh, Michael Silver, Theresa Jacob","doi":"10.1002/ajmg.b.33032","DOIUrl":"10.1002/ajmg.b.33032","url":null,"abstract":"<p><p>Prader-Willi Syndrome (PWS), a rare genetic disorder, affects development and behavior, frequently resulting in self-injury, aggression, hyperphagia, oppositional behavior, impulsivity, and over-activity, causing significant morbidity. Currently, limited therapeutic options are available to manage these neuropsychiatric manifestations. A randomized, placebo-controlled trial was conducted to assess the efficacy of guanfacine-extended release (GXR) in reducing aggression and self-injury in individuals with PWS. Subjects with a diagnosis of PWS, aged 6-35 years with moderate to severe aggressive and/or self-injurious behavior, as determined by the clinical global impression (CGI)-Severity scale, were included in an 8-week double-blind, placebo-controlled, fixed-flexible dose clinical trial of GXR, that was followed by an 8-week open-label extension phase. Validated behavioral instruments and physician assessments measured the efficacy of GXR treatment, its safety, and tolerability. GXR was effective in reducing aggression/agitation and hyperactivity/noncompliance, as measured by the Aberrant Behavior Checklist (ABC) scales (p = 0.03). Overall aberrant behavior scores significantly reduced in the GXR arm. Aggression, as measured by the modified overt aggression scale (MOAS) also showed a significant reduction. Skin-picking lesions, as measured by the self injury trauma (SIT) scale, decreased in response to GXR. No serious adverse events were experienced by any of the study participants. Fatigue/sedation was the only adverse event significantly associated with GXR. The GXR group demonstrated significant overall clinical improvement, as measured by the CGI-Improvement (CGI-I) scale (p < 0.01). Findings of this pragmatic trial strongly support the use of GXR for the treatment of aggression, skin picking, and hyperactivity in children, adolescents, and adults with PWS.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":" ","pages":"62-70"},"PeriodicalIF":1.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of SLC39A8.p.(Ala391Thr) in Schizophrenia Symptom Severity and Cognitive Ability: Cross-Sectional Studies of Schizophrenia and the General UK Population","authors":"Sophie E. Smart,&nbsp;Sophie E. Legge,&nbsp;Eilidh Fenner,&nbsp;Antonio F. Pardiñas,&nbsp;Grace Woolway,&nbsp;Amy J. Lynham,&nbsp;Valentina Escott-Price,&nbsp;Jeremy Hall,&nbsp;Lawrence Wilkinson,&nbsp;Peter Holmans,&nbsp;Michael C. O'Donovan,&nbsp;Michael J. Owen,&nbsp;James T.R. Walters","doi":"10.1002/ajmg.b.33037","DOIUrl":"10.1002/ajmg.b.33037","url":null,"abstract":"<p>The missense SNP NC_000004.12:g.102267552C&gt;T (also known as SLC39A8.p.(Ala391Thr), rs13107325) in <i>SLC39A8</i> encodes a zinc transporter. This SNP has been linked to schizophrenia and is the likely causal variant for one of the genome-wide association loci associated with the disorder. Using regression analyses, we tested whether the schizophrenia-risk allele at p.(Ala391Thr) was associated with schizophrenia-related phenotypes, including positive, negative, and disorganized symptoms, cognitive ability, educational attainment, and age of psychosis onset, within three schizophrenia cohorts (combined <i>N</i> = 1232) and, with equivalent phenotypes, in a sample of population controls (UK Biobank, <i>N</i> = 355,069). We also used the population controls to test for associations with rare protein-truncating and deleterious missense variants within <i>SLC39A8</i>. Within the schizophrenia cohorts, after correction for multiple testing, p.(Ala391Thr) was not significantly associated with any schizophrenia-related phenotypes. In the unaffected participants from the UK Biobank, the schizophrenia-risk allele at p.(Ala391Thr) was associated with significantly poorer cognitive ability and fluid intelligence, a lower probability of obtaining GCSEs or a degree-level qualification, and fewer years in education. There was no association between p.(Ala391Thr) and self-reported psychotic experiences in this cohort. Rare variants in <i>SLC39A8</i> were nominally associated with poorer cognitive ability, but these associations did not survive correction for multiple testing. The schizophrenia-risk allele was associated with poorer cognitive ability, but not psychotic experiences, in a volunteer sample drawn from the general population. We found no evidence that p.(Ala391Thr) was associated with symptom severity in schizophrenia. To understand the impact of rare variants in <i>SLC39A8</i> on cognitive impairment, larger independent samples are required.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"198 7","pages":"135-146"},"PeriodicalIF":1.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics of Response to ECT, TMS, Ketamine and Esketamine","authors":"Clio E. Franklin,&nbsp;Murat Altinay,&nbsp;Kala Bailey,&nbsp;Mahendra T. Bhati,&nbsp;Brent R. Carr,&nbsp;Susan K. Conroy,&nbsp;Khurshid Khurshid,&nbsp;William M. McDonald,&nbsp;Brian J. Mickey,&nbsp;James W. Murrough,&nbsp;Sean M. Nestor,&nbsp;Thomas Nickl-Jockschat,&nbsp;Irving M. Reti,&nbsp;Gerard Sanacora,&nbsp;Nicholas T. Trapp,&nbsp;Biju Viswanath,&nbsp;Jesse H. Wright,&nbsp;Peter P. Zandi,&nbsp;James B. Potash","doi":"10.1002/ajmg.b.33038","DOIUrl":"10.1002/ajmg.b.33038","url":null,"abstract":"<p>Treatment-resistant mood disorders are often managed with intensive interventions that include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), ketamine, and esketamine, but the role of genetics in clinical response to those interventions is yet to be clearly determined. Here, we review the current literature on the genetics of response to these treatment modalities. To date, the limited number of studies done to investigate genetic predictors of treatment response have primarily focused on single variants in candidate genes, and none of these have been consistently reproducible. The majority of candidate gene studies examine the effect of variants in the <i>COMT</i> and <i>BDNF</i> genes on treatment response. There are a limited number of genome-wide association studies (GWAS) looking at treatment response, though they are almost all underpowered, with only one study including a sample size &gt; 1000. As a result, there have been few single nucleotide polymorphisms (SNPs) found to be associated with treatment response at a statistically significant level, all in genes other than <i>COMT</i> and <i>BDNF</i>. The challenge is now to generate data from a large group of patients undergoing these therapies in order to more robustly assess the genetic factors affecting treatment response. This will not only help establish genetic predictors of response, but also potentially develop differential predictors of response to available treatments, which could provide clinicians with critical information to aid in deciding which treatment modality to recommend for treatment-resistant depression. We are currently pursuing such a strategy in our 50-site worldwide Gen-ECT-ic consortium.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"198 7","pages":"88-102"},"PeriodicalIF":1.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome Sequencing Uncovers Additional Findings in Phelan-McDermid Syndrome","authors":"Rachel Gore Moses,&nbsp;Morgan Similuk,&nbsp;Alexandra Hehn,&nbsp;Rylee Duncan,&nbsp;Margaret Pekar,&nbsp;Eliza Gordon-Lipkin,&nbsp;Maria T. Acosta,&nbsp;Deena Zeltser,&nbsp;Nadjalisse Reynolds-Lallement,&nbsp;Latha Soorya,&nbsp;Mustafa Sahin,&nbsp;Tess Levy,&nbsp;Alexander Kolevzon,&nbsp;Joseph D. Buxbaum,&nbsp;Elizabeth Berry-Kravis,&nbsp;Craig M. Powell,&nbsp;Jonathan A. Bernstein,&nbsp;Mari Tokita,&nbsp;Bryce A. Seifert,&nbsp;Rajarshi Ghosh,&nbsp;Magdalena A. Walkiewicz,&nbsp;Audrey Thurm","doi":"10.1002/ajmg.b.33036","DOIUrl":"10.1002/ajmg.b.33036","url":null,"abstract":"<p>Phelan-McDermid syndrome (PMS) is a genetic condition caused by deletions of chromosome 22q13.3 or pathogenic variants in the <i>SHANK3</i> gene. Neurologic features typically include intellectual disability, autism spectrum disorder, hypotonia, and absent speech, though there is considerable variability even among individuals with the same molecular cause. This prospective study aimed to explore the utility of genome sequencing to identify additional molecular diagnoses that may contribute to variability in a cohort of patients with PMS. Twenty probands diagnosed with PMS (60% with a 22q13 deletion, 40% with a <i>SHANK3</i> variant) underwent trio or duo genome sequencing and chromosomal microarray. This analysis identified a second molecular finding associated with a neurological condition in 3/20 participants. Molecular diagnoses related to neurological phenotypes included: (1) spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant (SMALED2A), (2) spastic paraplegia 7, and (3) 16p11.2 deletion syndrome. Five additional new molecular diagnoses were associated with a clinically actionable secondary or incidental finding. This exploratory study provides early evidence for the potential utility of expanded sequencing among individuals with PMS, even for those without phenotypic features outside of the expected range.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"198 7","pages":"126-134"},"PeriodicalIF":1.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}