Research Library
Browse scientific publications and research papers about HNRNP-Related Neurodevelopmental Disorders, organized by gene.
Key Papers
Foundational research papers establishing the HNRNP-RNDD field.
Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders
Gillentine et al. show analysis of large cohorts to identify novel disease-related HNRNP genes. Includes HNRNPAB, HNRNPD, HNRNPH1, HNRNPH2, HNRNPH3, HNRNPK, HNRNPR, SYNCRIP/HNRNPQ, HNRNPU, HNRNPUL1, and HNRNPUL2. This is the first publication linking the HNRNP-RNDDs.
Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins
Huelga et al. performed CLIP-seq and identified that more than half of alternative splicing events are regulated by multiple hnRNPs and that some combinations of hnRNPs have synergy or act antagonistically. This paper highlights the importance of the complementary and compensatory relationships between hnRNPs.
GeneReviews
Comprehensive clinical resources for healthcare providers.
GeneReviews: HNRNPH2-Related Neurodevelopmental Disorder
GeneReviews article discussing HNRNPH2-RNDD. This is a great resource to show clinicians.
GeneReviews: HNRNPU-Related Neurodevelopmental Disorder
GeneReviews article describing HNRNPU-RNDD. This is a great resource for clinicians.
GeneReviews: Au-Kline syndrome
GeneReviews article describing Au-Kline syndrome. This is a great resource for clinicians.
HNRNPC
See all HNRNPC papersHNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder
Niggl et al. describe 13 individuals with HNRNPC-RNDD, RNA-seq results, and iPSC functional studies.
HNRNPG/RBMX
See all RBMX/HNRNPG papersGustavson syndrome is caused by an in-frame deletion in RBMX associated with potentially disturbed SH3 domain interactions
Johansson et al. publish molecular findings of a large family with Gustavson syndrome, originally described in 1993. They find that there is an indel in RBMX that results in altered SH3 domain interactions.
Comment on Gustavson syndrome is caused by an in-frame deletion in RBMX associated with potentially disturbed SH3 domain interactions
Gillentine comments on the novel SH3 domain interaction dysregulation described by Johanssen et al.
Deletion of RBMX RGG/RG motif in Shashi-XLID syndrome leads to aberrant p53 activation and neuronal differentiation defects
Cai et al. performed molecular studies in cells from modeling individuals with Shashi-type ID. They find that RBMX-depleted cells have alterations in the p53 signaling pathway and changes splicing of specific transcripts. The find that loss of function of the RGG/RG motif likely causes Shashi-type ID.
RBMX family proteins connect the fields of nuclear RNA processing, disease and sex chromosome biology
Review discussing the functions of RBMX.
The RBMX gene as a candidate for the Shashi X-linked intellectual disability syndrome
First report of Shashi-type ID.
HNRNPH1
See all HNRNPH1 papersVariants in HNRNPH1 are associated with high myopia in humans and ocular coloboma in zebrafish
Ouyang et al. describe how variants in HNRNPH1 are associated with myopia (nearsightedness) and coloboma.
Interconnected Gene Networks Underpin the Clinical Overlap of HNRNPH1-Related and Rubinstein-Taybi Intellectual Disability Syndromes
Larizza et al. discuss the overlapping changes in gene expression between HNRNPH1-RNDD and another disorder, Rubinstein-Taybi syndrome.
HNRNPH1-related syndromic intellectual disability: Seven additional cases suggestive of a distinct syndromic neurodevelopmental syndrome
Reichert et al. identify features that make HNRNPH1-RNDD and HNRNPH2-RNDD distinct syndromes.
Mutations disrupting neuritogenesis genes confer risk for cerebral palsy
Identify variants among individuals with cerebral palsy, including one HNRNPH1-RNDD individual.
Evidence for HNRNPH1 being another gene for Bain type syndromic mental retardation
Describe a male with HNRNPH1-RNDD (although still considered HNRNPH2-RNDD at time of publication).
HNRNPH2
See all HNRNPH2 papersPreclinical evaluation of antisense oligonucleotide therapy in a mouse model of HNRNPH2-related neurodevelopmental disorder
Korff et al. discuss preclinical evaluation of the ongoing HNRNPH2-RNDD ASO therapy in a mouse model.
Reactivation of Human X-Linked Gene and Stable X-Chromosome Inactivation Observed in Generation and Differentiation of iPSCs from a Female Patient with HNRNPH2 Mutation
Chen et al. discuss their iPSC model of HNRNPH2-RNDD modeling c.340C>T.
A murine model of hnRNPH2-related neurodevelopmental disorder reveals a mechanism for genetic compensation by Hnrnph1
Korff et al. establish and describe the mouse model for HNRNPH2-RNDD, identifying compensation by HNRNPH1.
Motor phenotypes associated with genetic neurodevelopmental disorders
The authors discuss motor phenotypes among multiple rare neurodevelopmental disorders, including HNRNPH2-RNDD.
A Prospective, Longitudinal Study of Caregiver-Reported Adaptive Skills and Function of Individuals with HNRNPH2-related Neurodevelopmental Disorder
Davis et al. discuss caregiver-reports of adaptive skills and function among individuals with HNRNPH2-RNDD.
Rett-like Phenotypes in HNRNPH2-Related Neurodevelopmental Disorder
Gonzalez et al. describe the overlapping features of Rett syndrome and HNRNPH2-RNDD.
A new Karyopherin-β2 binding PY-NLS epitope of HNRNPH2 linked to neurodevelopmental disorders
Gonzalez et al. discuss variants in hnRNPH2 that are in nuclear localization signal.
Variant-specific effects define the phenotypic spectrum of HNRNPH2-associated neurodevelopmental disorders in males
Kreienkamp et al. describe males with HNRNPH2-RNDD.
A disease-causing variant in HNRNPH2 inherited from an unaffected mother with skewed X-inactivation
Identified a maternally inherited variant in a male in HNRNPH2 due to skewed X-inactivation.
Detailed Clinical and Psychological Phenotype of the X-linked HNRNPH2-Related Neurodevelopmental Disorder
Describe cohort of individuals with HNRNPH2-RNDD.
Cross-sectional, quantitative analysis of motor function in females with HNRNPH2-related disorder
Salazar et al. discuss the differences in motor function among individuals with HNRNPH2-RNDD.
Bain type of X-linked syndromic mental retardation in a male with a pathogenic variant in HNRNPH2
Describe a male with HNRNPH2-RNDD.
Missense variants in the Arg206 residue of HNRNPH2: Further evidence of causality and expansion of the phenotype
Peron et al. further investigate recurrent HNRNPH2 p.Arg206 variants.
Bain type of X-linked syndromic mental retardation in boys
Harmsen et al. describe males with HNRNPH2-RNDD.
Two additional males with X-linked, syndromic mental retardation carry de novo mutations in HNRNPH2
Jepsen et al. describe two additional males with HNRNPH2-RNDD.
Variants in HNRNPH2 on the X Chromosome Are Associated with a Neurodevelopmental Disorder in Females
First report of HNRNPH2-RNDD.
PTBP1/HNRNPI
See all PTBP1 papersPTBP1 variants displaying altered nucleocytoplasmic distribution are responsible for a neurodevelopmental disorder with skeletal dysplasia
First report of PTBP1 (HNRNPI)-RNDD.
HNRNPK
See all HNRNPK papersA Novel Intronic Variant in the KH3 Domain of HNRNPK Leads to a Mild Form of Au-Kline Syndrome
Mingoia et al. describe a novel splice variant that causes mild Au-Kline syndrome.
Prenatal diagnosis of a de novo pathogenic HNRNPK variant in a Chinese fetus with abnormal ultrasound soft markers: a case report
Zhu et al. describe a prenatal case of Au-Kline syndrome.
An HNRNPK-specific DNA methylation signature makes sense of missense variants and expands the phenotypic spectrum of Au-Kline syndrome
Established the methylation signature of Au-Kline syndrome and of those with HNRNPK variants that have a different pattern.
Exome sequencing reveals predominantly de novo variants in disorders with intellectual disability (ID) in the founder population of Finland
Jarvela et al. describe their findings from 39 families with ID and identify an HNRNPK variant.
Diagnostic utility of integrated analysis of exome and transcriptome: Successful diagnosis of Au-Kline syndrome in a patient with submucous cleft palate, scaphocephaly, and intellectual disabilities
Yamada et al describe use of both exome and transcriptome analysis to diagnosis Au-Kline syndrome.
Okamoto syndrome has features overlapping with Au-Kline syndrome and is caused by HNRNPK mutation
Describes an individual with Okamoto syndrome, which overlaps with Au-Kline syndrome and is also caused by HNRNPK variants, resulting in Au-Kline-Okamoto syndrome.
Phenotypic spectrum of Au-Kline syndrome: a report of six new cases and review of the literature
Au et al. describe six novel HNRNPK-RNDD (Au-Kline syndrome) patients and review the literature.
A case of atypical Kabuki syndrome arising from a novel missense variant in HNRNPK
Miyake et al. describe a recurrent HNRNPK variant that has been mistaken for Kabuki syndrome.
A de novo frameshift in HNRNPK causing a Kabuki-like syndrome with nodular heterotopia
Report individual with Kabuki syndrome and HNRNPK variant.
GeneMatcher aids in the identification of a new malformation syndrome with intellectual disability, unique facial dysmorphisms, and skeletal and connective tissue abnormalities caused by de novo variants in HNRNPK
First report of Au-Kline syndrome.
HNRNPR
See all HNRNPR papersHNRNPR Variants that Impair Homeobox Gene Expression Drive Developmental Disorders in Humans
Duijkers et al. describe the first individuals with truncating or missense variants in the HNRNPR gene in the C terminal region of the hnRNPR protein.
SYNCRIP/HNRNPQ
See all SYNCRIP papersPosttranscriptional Control of Neural Progenitors Temporal Dynamics During Neocortical Development by Syncrip
Wu et al. describe their mouse model that conditionally knocks out syncrip in radial glia, resulting in behavioral and molecular changes related to neuronal migration.
An expansion of the phenotype in individuals with SYNCRIP-Related Neurodevelopmental Disorder
Shafiq et al. describe ten novel individuals with SYNCRIP-RNDD to expand the known phenotype.
Comparison of first-tier whole-exome sequencing with a multi-step traditional approach for diagnosing paediatric outpatients: An Italian prospective study
Rosina et al. describe their findings from 125 individuals with exome sequencing and identify a SYNCRIP variant.
Identification of a Mosaic Variant in the SYNCRIP Gene Causing Foetal Periventricular Nodular Heterotopia, Abnormal Sulcation and Infratentorial Anomaly
Birnbaum et al describe the first prenatal, mosaic SYNCRIP variant.
Further evidence for de novo variants in SYNCRIP as the cause of a neurodevelopmental disorder
Semino et al. describe three novel individuals with SYNCRIP-RNDD and highlight their phenotypic features that are likely due to haploinsufficiency.
The cytoplasmic SYNCRIP mRNA interactome of mammalian neurons
The authors describe the SYNCRIP mRNA interactome from primary rat cortical neurons using iCLIP, identifying targets that are involved in neurogenesis, neuronal migration, and neurite outgrowth.
Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes
Guo et al. describe findings from large autism cohorts, including one of the first identified SYNCRIP-RNDD patients.
The phenotypic spectrum of proximal 6q deletions based on a large cohort derived from social media and literature reports
Engwerda et al. describe individuals with 6q deletions, which can include SYNCRIP.
HNRNPU
See all HNRNPU papersExpanding the Phenotypic Spectrum of HNRNPU-Related Disorder, Documenting the First Familial Presentation and Comprehensive Review
Hodgson et al. expand the phenotypic spectrum of HNRNPU-RNDD and describe an inherited case.
EpiSignature Utility for Variant of Uncertain Significance Reclassification in an Apparently Atypical Presentation of HNRNPU-Related Neurodevelopmental Disorder: A Case Report
Zuelke et al. describe the utility of the episignature for HNRNPU-RNDD and describe a predicted loss of function variant that does not have the same signature.
Severe pharyngeal stenosis and laryngomalacia in an individual of HNRNPU-related neurodevelopmental disorder associated with a novel nonsense variant
Sasaki et al. describe a novel patient with HNRNPU-RNDD.
Neurodevelopmental deficits and cell-type-specific transcriptomic perturbations in a mouse model of HNRNPU haploinsufficiency
Dugger et al. describe the mouse model they established of HNRNPU-RNDD.
DNA methylation episignature and comparative epigenomic profiling of HNRNPU-related neurodevelopmental disorder
Rooney et al. describe the methylation signature for HNRNPU-RNDD.
Germline pathogenic variants in HNRNPU are associated with alterations in blood methylome
Lee et al describe a methylation signature for HNRNPU-RNDD.
HNRNPU's multi-tasking is essential for proper cortical development
Review discussing the importance of HNRNPU in neuronal development.
Deficiency of the Heterogeneous Nuclear Ribonucleoprotein U locus leads to delayed hindbrain neurogenesis
The authors discuss their mouse model of HNRNPU-RNDD and find that brain development is disrupted.
Expanding the phenotype of HNRNPU-related neurodevelopmental disorder with emphasis on seizure phenotype and review of literature
Taylor et al., describe 17 novel probands with HNRNPU-RNDD, including those with recurrent variants.
Evidence of shared transcriptomic dysregulation of HNRNPU-related disorder between human organoids and embryonic mice
Ressler et al. describe the transcriptional differences in HNRNPU-RNDD model organoids and embryonic mice.
Clinical next generation sequencing in developmental and epileptic encephalopathies: Diagnostic relevance of data re-analysis and variants re-interpretation
Salinas et al. describe their findings from reanalyzing data from 55 individuals with epilepsy, including an individual with HNRNPU-RNDD.
De novo frameshift variants of HNRNPU in patients with early infantile epileptic encephalopathy: Two case reports and literature review
Song et al. describe two novel individuals with HNRNPU-RNDD.
Pharmacological Treatment of Severe Breathing Abnormalities in a Case of HNRNPU Epileptic Encephalopathy
Spagnoli et al. describe treatment of breathing abnormalities in an individual with HNRNPU-RNDD.
Clinical findings of 21 previously unreported probands with HNRNPU-related syndrome and comprehensive literature review
Durken et al. describe 21 novel HNRNPU-RNDD probands and review the literature.
Heterozygous HNRNPU variants cause early onset epilepsy and severe intellectual disability
Bramswig et al. are among the first to publish HNRNPU-RNDD probands (n = 7) with epilepsy and severe intellectual disability.
De novo mutations in HNRNPU result in a neurodevelopmental syndrome
Yates et al., describe seven HNRNPU-RNDD probands from the DDD study.
Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU
Depienne et al. describe individuals with variants in HNRNPU and how they compare to the larger 1q43q44 microdeletion syndrome.
Clinical and molecular characterization of de novo loss of function variants in HNRNPU
Luduc et al. describe four novel individuals with HNRNPU-RNDD with loss of function variants.
Candidate HNRNPs
Research on genes being investigated as potential HNRNP-RNDDs.
Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes
Multiple de novo variants identified in the SPARK cohort, highlights HNRNPUL2.
Expanding the spectrum of microdeletion 4q21 syndrome: a partial phenotype with incomplete deletion of the minimal critical region and a new association with cleft palate and Pierre Robin sequence
Bhoj et al describe patients with 4q21 deletion syndrome, which includes HNRNPD and HNRNPDL in the critical region.
Microdeletion at chromosome 4q21 defines a new emerging syndrome with marked growth restriction, mental retardation and absent or severely delayed speech
Bonnet et al describe patients with 4q21 deletion syndrome, which includes HNRNPD and HNRNPDL in the critical region.
Multiple HNRNPs and Reviews
Overview papers covering multiple HNRNP genes and general reviews.
The HNRNPs and neurodevelopmental disorders
Gillentine reviews the HNRNP genes and their roles in neurodevelopmental disorders.
Prospective study to analyze the yield and clinical impact of trio exome sequencing in 137 Indian children with autism spectrum disorder
Bajaj et al. investigate genetic causes of 137 children with autism spectrum disorder, identifying one HNRNPDL variant.
hnRNPs: roles in neurodevelopment and implication for brain disorders
Tilliole et al. review the roles of hnRNPs in neurodevelopment and how disruption of them leads to disease.
Identification of RNA N6-methyladenosine regulation in epilepsy: Significance of the cell death mode, glycometabolism, and drug reactivity
Liu et al. describe their findings of genes involved in m6A regulation (including HNRNPC and RBMX) and their risk in epilepsy.
Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
Wang et al. identify several individuals with HNRNP variants from large cohort studies.
The hnRNP family: insights into their role in health and disease
Review covering structure, function, and role in disease of hnRNP encoding genes.
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