Forschung & Studien

Wissenschaftliche Veröffentlichungen

Diese Liste wird automatisch aus der medizinischen Literaturdatenbank PubMed zusammengestellt. Sie zeigt neue wissenschaftliche Veröffentlichungen, die den Begriff RNU4-2 enthalten. Die Inhalte sind überwiegend englischsprachig und wurden von uns nicht redaktionell geprüft oder übersetzt.

2026

• Whole-genome discovery of pathogenic snRNA variants and efficient extended-exome screening
  Juli 26, 2026 von Yuka Nakano
  Pathogenic variants in small nuclear RNA (snRNA) genes have recently emerged as a major cause of Mendelian disorders, particularly neurodevelopmental disorders, yet they remain difficult to detect in routine diagnostics because conventional whole-exome sequencing (WES) does not capture snRNA loci. Here, we reanalyzed whole-genome sequencing (WGS) data from 1,578 unsolved probands and identified pathogenic variants […]
• Recurrent RNU4-2 n.64_65insT variant in ReNU syndrome identified in exome-negative cases
  Juli 8, 2026 von Takuya Hiraide
  CONCLUSIONS: Our findings underscore RNU4-2 as a major cause of NDDs in ES-negative cases and further delineate the phenotypic spectrum of ReNU syndrome. Recognition of the characteristic "lip and philtrum gestalt" serves as a vital clinical clue, prompting targeted genetic evaluation for this frequently overlooked disorder.
• Multimodal Sequencing and Reanalysis Approaches to End the Diagnostic Odyssey of Individuals with Suspected Rare Monogenic Diseases
  Juni 26, 2026 von Catherine A Brownstein
  CONCLUSIONS: This small pilot cohort is not intended to estimate general diagnostic yield, but it demonstrates that a coordinated multimodal framework can reveal different sources of added value, including structural variant discovery, orthogonal functional support, and reinterpretation of existing short-read data as knowledge evolves. These findings underscore that archived short-read exome and genome data can […]
• ReNU Syndrome and the RNU4-2 Mutation: A Missed Cause of Childhood Neurodevelopmental Delay
  Juni 12, 2026 von Jawairya Muhammad Hussain
  ReNU syndrome is a rare but increasingly recognized syndromic neurodevelopmental disorder caused by heterozygous de novo variants in the non-coding gene RNU4-2, which encodes the U4 small nuclear RNA (snRNA), a critical component of the major spliceosome. Recurrent pathogenic variants cluster within an 18-base-pair critical region of RNU4-2 and disrupt normal spliceosome function by altering […]
• Author Correction: Biallelic variants in the noncoding RNA gene RNU4-2 cause a recessive neurodevelopmental syndrome with distinct white matter changes
  Mai 18, 2026 von Rocio Rius
  No abstract
• A new era for the dark genome
  April 13, 2026 von Merel Stemerdink
  A landmark study by Quinodoz et al. revealed that variants in noncoding small nuclear RNA genes, RNU4-2 and four RNU6 paralogs, represent a previously unrecognized cause of autosomal dominant retinitis pigmentosa. This uncovers pleiotropy in RNU4-2 variants and expands the genetic architecture of Mendelian disease into the 'dark genome'.
• Saturation editing of RNU4-2 reveals distinct dominant and recessive disorders
  April 8, 2026 von Joachim De Jonghe
  Recently, de novo variants in an 18-nucleotide region in the centre of RNU4-2 were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder that is predicted to affect tens of thousands of individuals worldwide^(1,2). RNU4-2 is a non-protein-coding gene that is transcribed into the U4 small nuclear RNA component of the major spliceosome³. ReNU syndrome […]
• Biallelic variants in the noncoding RNA gene RNU4-2 cause a recessive neurodevelopmental syndrome with distinct white matter changes
  April 8, 2026 von Rocio Rius
  Genetic variants in RNU4-2, which is transcribed into the U4 small nuclear RNA component of the major spliceosome, were recently shown to cause ReNU syndrome, a prevalent dominant neurodevelopmental disorder (NDD). These variants almost exclusively arise de novo and cluster within 18 nucleotides of RNU4-2. Here we describe a new recessive NDD associated with homozygous […]
• Biallelic variants in RNU2-2 cause the most prevalent known recessive neurodevelopmental disorder
  März 30, 2026 von Daniel Greene
  We recently showed that mutations in the snRNA genes RNU4-2 and RNU2-2 are prevalent causes of dominant neurodevelopmental disorders (NDDs). Here, by genetic association, we demonstrate the existence of a recessive form of RNU2-2 syndrome. We inferred a log Bayes factor for a recessive model of association of 18.2. Conditional on that model, 17 rare […]
• Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies
  März 30, 2026 von Elsa Leitão
  Small nuclear RNAs (snRNAs) are essential components of the spliceosome. De novo variants in snRNA genes RNU4-2 (ReNU syndrome), RNU5B-1 and RNU2-2 have been linked to dominant neurodevelopmental disorders (NDDs), revealing a large unexpected contribution of noncoding RNA genes to genetic diseases. Here, through international collaborations, we analyze systematically 200 potentially functional snRNA genes in […]
• First Identification of a Heterozygous RNU4-2 and RNU4-1 Deletion Associated With Fetal Urogenital and Anorectal Malformations
  März 20, 2026 von Mario Abaji
  What is already known about this topic?◦Pathogenic sequence variants in RNU4‐2 cause ReNU syndrome characterized by severe neurodevelopmental disorder, microcephaly, and brain malformations.◦This syndrome has been recently described in hundreds of individuals. Urogenital malformations have not been described as part of the ReNU syndrome spectrum.What does this study add?◦We report the first identification of a […]
• Exploring the Impact of RNU4-2 Defects on Neurodevelopmental Disorders in a Korean Population
  Februar 24, 2026 von Juhyeon Hong
  Neurodevelopmental disorders (NDDs) often remain unexplained due to limited assessment of non-coding genomic elements. Motivated by recent reports implicating RNU4-2, which encodes a spliceosomal small nuclear RNA (snRNA), we analyzed whole-genome sequencing data from 15 450 Korean individuals, including 2797 unrelated NDD probands. Rare pathogenic RNU4-2 variants were identified in 20 probands (0.72%), including 17 […]
• Summary of the Inaugural ReNU Hope Conference and Scientific Symposium, July 23-25, 2025, Long Island, New York
  Februar 19, 2026 von Kelsey Crocker
  The inaugural ReNU Hope Conference and Scientific Symposium was held from July 23-25, 2025 in Long Island, New York. This historic conference brought together the researchers responsible for the groundbreaking discovery of RNU4-2/ReNU syndrome, families, scientists, clinicians, trainees, therapeutic developers, and industry leaders from around the world. The key themes that emerged included: (1) Early […]
• Longitudinal Behavior Phenotype Hallmarks in RNU4-2 Syndrome: Implications for Clinical Management
  Februar 13, 2026 von Paola Francesca Ajmone
  Pathogenic variants in the non-coding spliceosomal gene RNU4-2 underlie ReNU syndrome, one of the most prevalent monogenic causes of neurodevelopmental disorders, accounting for ~0.4% of cases. Despite increasing recognition, little is known about the longitudinal behavioral and neuropsychiatric phenotype of affected individuals. We report two patients with RNU4-2 variants, providing a comprehensive description of their […]
• ReNU Syndrome due to a de novo RNU4-2 Variant as a Novel Genetic Cause of Proteinuria
  Februar 2, 2026 von William Morello
  Proteinuria has been linked to several genetic disorders, providing valuable insights into its pathophysiology. ReNU syndrome, a recently described condition caused by heterozygous variants in the RNU4-2 gene, is characterized by intellectual disability, microcephaly, and multisystemic features. Kidney involvement has been reported exclusively as anatomical abnormalities. Here, we presented a girl with isolated proteinuria and […]
• Correspondence on "Deep phenotyping of 11 individuals with pathogenic variants in RNU4-2 reveals a clinically recognizable syndrome" by Valenzuela et al
  Januar 23, 2026 von Zarnab Saleem
  No abstract
• Response to Saleem et al
  Januar 23, 2026 von Irene Valenzuela
  No abstract
• De novo and inherited dominant variants in U4 and U6 snRNA genes cause retinitis pigmentosa
  Januar 9, 2026 von Mathieu Quinodoz
  Small nuclear RNAs (snRNAs) combine with specific proteins to generate small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. U4 snRNA forms a duplex with U6 and, together with U5, contributes to the tri-snRNP spliceosomal complex. Variants in RNU4-2, which encodes U4, have recently been implicated in neurodevelopmental disorders. Here we show that heterozygous […]
• Monoallelic and biallelic RNU4-2 variants in neurodevelopmental disorders
  Dezember 17, 2025 von Yukina Hayashi
  The accurate removal of intronic sequences from pre-mRNA by the spliceosome is essential for correct gene expression, with small nuclear RNAs (snRNAs) such as U4 playing structural and regulatory roles in catalyzing this. De novo variants in the highly constrained critical region including the T-loop region of RNU4-2 have been linked to ReNU syndrome, a […]
• Deep phenotyping of 11 individuals with pathogenic variants in RNU4-2 reveals a clinically recognizable syndrome
  Dezember 6, 2025 von Irene Valenzuela
  No abstract

2025

• ReNU Syndrome due to a de novo RNU4-2 Variant as a Novel Genetic Cause of Proteinuria
  Februar 2, 2026 von William Morello
  Proteinuria has been linked to several genetic disorders, providing valuable insights into its pathophysiology. ReNU syndrome, a recently described condition caused by heterozygous variants in the RNU4-2 gene, is characterized by intellectual disability, microcephaly, and multisystemic features. Kidney involvement has been reported exclusively as anatomical abnormalities. Here, we presented a girl with isolated proteinuria and […]
• Prenatal Evaluation of RNU4-2 Variants in Fetuses With Central Nervous System Anomalies
  Dezember 26, 2025 von Yiyao Chen
  Fetal central nervous system (CNS) anomalies are among the most common congenital malformations, yet the overall prenatal diagnostic yield of current genetic testing remains below 40%. Variants in RNU4-2, a non-coding gene encoding the U4 small nuclear RNA (snRNA), have recently been linked to a novel highly recurrent dominant neurodevelopmental disorder termed ReNU syndrome. While […]
• Monoallelic and biallelic RNU4-2 variants in neurodevelopmental disorders
  Dezember 17, 2025 von Yukina Hayashi
  The accurate removal of intronic sequences from pre-mRNA by the spliceosome is essential for correct gene expression, with small nuclear RNAs (snRNAs) such as U4 playing structural and regulatory roles in catalyzing this. De novo variants in the highly constrained critical region including the T-loop region of RNU4-2 have been linked to ReNU syndrome, a […]
• Deep phenotyping of 11 individuals with pathogenic variants in RNU4-2 reveals a clinically recognizable syndrome
  Dezember 6, 2025 von Irene Valenzuela
  No abstract
• Reanalysis of Undiagnosed Neurodevelopmental Disorder Cases: From RNU4-2 Variants to Clinical Phenotypes
  Oktober 23, 2025 von Pasquale Di Letto
  BACKGROUND AND OBJECTIVES: Neurodevelopmental disorders (NDDs) are often the results of genetic factors, whose identification and key role in their etiology may be elusive. Despite advancements in genetic testing, many cases remain unsolved. Single-nucleotide variants in a critical 18-bp region of the noncoding gene RNU4-2, a crucial component of the spliceosome complex, have been recently […]
• Genome sequencing for the diagnosis of intellectual disability as a paradigm for rare diseases in the French healthcare setting: the prospective DEFIDIAG study
  Oktober 4, 2025 von Salima El Chehadeh
  CONCLUSIONS: As a first line test for ID diagnosis, WGS (including for solo situations) proved to be more effective than the reference strategy, in the context of real-life hospital settings in France.
• Systematic analysis of snRNA genes reveals frequent RNU2-2 variants in dominant and recessive developmental and epileptic encephalopathies
  September 15, 2025 von Elsa Leitão
  Variants in spliceosomal small nuclear RNA (snRNA) genes RNU4-2 (ReNU syndrome), RNU5B-1, and RNU2-2 have recently been linked to dominant neurodevelopmental disorders (NDDs), revealing a major, previously overlooked role for noncoding snRNAs in human disease. Here, we systematically analysed 200 potentially functional snRNA genes in a French cohort comprising 26,911 individuals with rare disorders and […]
• Biallelic variants in RNU2-2 cause the most prevalent known recessive neurodevelopmental disorder
  September 5, 2025 von Daniel Greene
  We recently showed that mutations in RNU4-2 and RNU2-2, two genes that are transcribed into small nuclear RNA (snRNA) components of the major spliceosome, are prevalent causes of dominant neurodevelopmental disorders (NDDs). By genetic association comparing 12,776 NDD cases with 56,064 controls, we now demonstrate the existence of a recessive form of RNU2-2 syndrome that, […]
• Identification of a pathogenic RNU4-2 variant in patients with mitochondrial disease: Broadening the spectrum of non-coding RNA gene variants in mitochondrial dysfunction
  Juli 22, 2025 von Kohta Nakamura
  Mitochondrial diseases are characterized by impaired energy production due to mitochondrial dysfunction. Despite advances in sequencing technologies, many cases remain genetically undiagnosed. We report two cases of mitochondrial disease harboring identical de novo variant in the non-coding RNA gene RNU4-2, previously associated with neurodevelopmental disorders. Re-analysis of whole genome sequencing data from 357 patients ascertained […]
• A Clinical Study of Nine Patients With ReNU Syndrome
  Juni 23, 2025 von Nobuhiko Okamoto
  ReNU syndrome, also known as neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language (NEDHAFA), is characterized by hypotonia, global developmental delay, intellectual disability with poor or absent speech, delayed motor development, feeding difficulties, short stature, seizures, and dysmorphic features. Neuroradiological abnormalities, including ventriculomegaly, hypoplasia of the corpus callosum, and a decreased white […]
• Assessment and treatment of osteoporosis in a patient with a neurodevelopmental disorder caused by a RNU4-2 pathogenic variant (ReNU syndrome)
  Juni 13, 2025 von Tess Holling
  A 16-yr-old male with a genetically undiagnosed neurodevelopmental disorder (NDD) was admitted to our outpatient clinic for skeletal assessment. DXA and HR-pQCT showed a severely reduced BMD and a pronounced reduction of trabecular and cortical bone mass. Lateral vertebral assessment identified multiple previously unrecognized vertebral fractures of the thoracic and lumbar spine. Laboratory tests indicated […]
• Analysis of R-loop forming regions identifies RNU2-2 and RNU5B-1 as neurodevelopmental disorder genes
  Mai 29, 2025 von Adam Jackson
  R-loops are DNA-RNA hybrid structures that may promote mutagenesis. However, their contribution to human Mendelian disorders is unexplored. Here we show excess de novo variants in genomic regions that form R-loops (henceforth, 'R-loop regions') and demonstrate enrichment of R-loop region variants (RRVs) in ribozyme, snoRNA and snRNA genes, specifically in rare disease cohorts. Using this […]
• Genotype-phenotype correlations and phenotypic expansion in a case series of ReNU syndrome associated with RNU4-2 variants
  Mai 24, 2025 von Yukiko Kuroda
  RNU4-2 encodes U4 small nuclear RNA (snRNA), a non-coding RNA forming the spliceosome complex via the U4/U6 snRNA duplex. RNU4-2 heterozygous variants cause ReNU syndrome, which is characterised by intellectual disability, developmental delay, epilepsy, short stature and distinctive dysmorphic features. ReNU syndrome accounts for 0.4-0.5% of all cases of developmental delay, and RNU4-2 variants are […]
• RNU4-2 monoallelic variants as a leading cause of syndromic neurodevelopmental disorder, including in patients with parental consanguinity
  Mai 24, 2025 von Aida M Bertoli-Avella
  We analysed rare variants in the non-coding RNU4-2 gene as a potential cause of neurodevelopmental disorder (NDD) and intellectual disability (ID) in a large cohort of individuals enriched for parental consanguinity.Genome sequencing (GS) data from 22 928 individuals in our Biodatabank were queried for rare, monoallelic variants in RNU4-2 From these, 4918 patients presented with […]
• Dominant variants in major spliceosome U4 and U5 small nuclear RNA genes cause neurodevelopmental disorders through splicing disruption
  Mai 16, 2025 von Caroline Nava
  The major spliceosome contains five small nuclear RNAs (snRNAs; U1, U2, U4, U5 and U6) essential for splicing. Variants in RNU4-2, encoding U4, cause a neurodevelopmental disorder called ReNU syndrome. We investigated de novo variants in 50 snRNA-encoding genes in a French cohort of 23,649 individuals with rare disorders and gathered additional cases through international […]
• Saturation genome editing of RNU4-2 reveals distinct dominant and recessive neurodevelopmental disorders
  April 29, 2025 von Joachim De Jonghe
  Recently, de novo variants in an 18 nucleotide region in the centre of RNU4-2 were shown to cause ReNU syndrome, a syndromic neurodevelopmental disorder (NDD) that is predicted to affect tens of thousands of individuals worldwide^(1,2). RNU4-2 is a non-protein-coding gene that is transcribed into the U4 small nuclear RNA (snRNA) component of the major […]
• Mutations in the small nuclear RNA gene RNU2-2 cause a severe neurodevelopmental disorder with prominent epilepsy
  April 10, 2025 von Daniel Greene
  The major spliceosome includes five small nuclear RNA (snRNAs), U1, U2, U4, U5 and U6, each of which is encoded by multiple genes. We recently showed that mutations in RNU4-2, the gene that encodes the U4-2 snRNA, cause one of the most prevalent monogenic neurodevelopmental disorders. Here, we report that recurrent germline mutations in RNU2-2 […]
• Expanding the mutational spectrum of ReNU syndrome: insights into 5' Stem-loop variants
  Februar 26, 2025 von Alessandro Bruselles
  A narrow spectrum of heterozygous variants in RNU4-2, encoding the small nuclear RNA (snRNA) U4, underlies ReNU syndrome, a neurodevelopmental disorder (NDD) characterized by moderate to severe developmental delay (DD), intellectual disability (ID), a distinctive facial gestalt, and multisystem involvement. Pathogenic variants have primarily been reported within an 18-nt critical region contributing to stabilizing the […]
• Reanalysis of whole genome sequencing ends a diagnostic Odyssey of neurodevelopmental disorders caused by RNU4-2 variants
  Februar 19, 2025 von Shiqi Fan
  No abstract
• Severe Osteoporosis in an Adult Subject with RNU4-2 Gene Mutation
  Februar 17, 2025 von Joshua Peñafiel-Sam
  Recent studies have shown that RNU4-2 pathogenic gene variants are among the most frequent causes of monogenic neurodevelopmental disorders. We present an adult patient with a pathogenic variant in the RNU4-2 gene associated with the presence of severe osteoporosis. A 19-year-old male diagnosed with ReNU syndrome after years of extensive evaluation for a history of […]

2024

• The Prevalence of RNU4-2-Associated Autosomal Dominant Intellectual Disability Syndrome
  Januar 5, 2025 von Kristen Barbour
  No abstract
• RNU4-2-Related Neurodevelopmental Disorder Is Associated With a Recognisable Facial Gestalt
  Oktober 22, 2024 von Jessica Rosenblum
  De novo heterozygous variants in RNU4-2, a component of the major spliceosome, were recently found to cause a novel neurodevelopmental disorder. Preliminary evidence suggests that this newly discovered syndrome is one of the most common monogenic causes of neurodevelopmental disorders. It is characterised by developmental delay and intellectual disability, microcephaly, short stature and hypotonia. However, […]
• The Face and Features of RNU4-2: A New, Common, Recognizable, Yet Hidden Neurodevelopmental Disorder
  Oktober 18, 2024 von Kristen Barbour
  CONCLUSIONS: Enhanced recognition of the RNU4-2 (n.64_65insT-common variant) phenotype, particularly the dysmorphic facial features, will facilitate earlier diagnosis. Distinctive characteristics will guide the selection of patients for testing able to detect RNU4-2 variants: genome sequencing or targeted gene testing. Furthermore, health and research systems may identify undiagnosed patients by querying databases for individuals exhibiting the […]
• Deep phenotyping of 11 individuals with pathogenic variants in RNU4-2 reveals a clinically recognizable syndrome
  Oktober 6, 2024 von Irene Valenzuela
  CONCLUSION: This work provides an improved characterization of the phenotypic spectrum of RNU4-2 syndrome across different age groups and demonstrates that thorough clinical assessment of patients with an NDD can be enhanced significantly for this novel syndrome.
• ReNU syndrome – a newly discovered prevalent neurodevelopmental disorder
  Oktober 2, 2024 von Vanessa F Burns
  Two recent papers have identified genetic variants in the noncoding gene RNU4-2 to cause a frequent neurodevelopmental disorder. This work will have a substantial impact on the rare disease community, leading to thousands of diagnoses worldwide. These studies also highlight the untapped diagnostic potential of noncoding regions.
• Mutations in the U2 snRNA gene RNU2-2P cause a severe neurodevelopmental disorder with prominent epilepsy
  September 16, 2024 von Daniel Greene
  The major spliceosome comprises the five snRNAs U1, U2, U4, U5 and U6. We recently showed that mutations in RNU4- 2, which encodes U4 snRNA, cause one of the most prevalent monogenic neurodevelopmental disorders. Here, we report that recurrent germline mutations in RNU2-2P , a 191bp gene encoding U2 snRNA, are responsible for a related […]
• RNU4-2 variants cause neurodevelopmental disorders
  August 12, 2024 von Safia Danovi
  No abstract
• De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome
  Juli 11, 2024 von Yuyang Chen
  Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes¹. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is […]
• Re-analysis of whole genome sequencing ends a diagnostic odyssey: Case report of an RNU4-2 related neurodevelopmental disorder
  Juni 11, 2024 von Rachel Schot
  Despite increasing knowledge of disease-causing genes in human genetics, approximately half of the individuals affected by neurodevelopmental disorders remain genetically undiagnosed. Part of this missing heritability might be caused by genetic variants outside of protein-coding genes, which are not routinely diagnostically investigated. A recent preprint identified de novo variants in the non-coding spliceosomal snRNA gene […]
• Mutations in the U4 snRNA gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders
  Mai 31, 2024 von Daniel Greene
  Most people with intellectual disability (ID) do not receive a molecular diagnosis following genetic testing. To identify new etiologies of ID, we performed a genetic association analysis comparing the burden of rare variants in 41,132 noncoding genes between 5,529 unrelated cases and 46,401 unrelated controls. RNU4-2, which encodes U4 small nuclear RNA, a critical component […]
• The Transcriptional Landscape of Coding and Noncoding RNAs in Recurrent and Nonrecurrent Colon Cancer
  Mai 4, 2024 von Ulrik Korsgaard
  A number of patients with colon cancer with local or local advanced disease suffer from recurrence and there is an urgent need for better prognostic biomarkers in this setting. Here, the transcriptomic landscape of mRNAs, long noncoding RNAs, snRNAs, small nucleolar RNAs (snoRNAs), small Cajal body-specific RNAs, pseudogenes, and circular RNAs, as well as RNAs […]
• De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders
  April 22, 2024 von Yuyang Chen
  Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes¹. Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA RNU4-2 as a novel syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), […]