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International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
Apr, 2025;85 (2): e70012.

A Novel KMT2E Splicing Variant as a Cause of O'Donnell-Luria-Rodan Syndrome With West Syndrome: Expansion of the Phenotype and Genotype.

Qianyun Cai, Fan Feng, Haijiao Wang, Yanmei Tian, Rong Luo, Fan Yang, Xiao Qian, Zhongjie Zhou
Author Information
  1. Qianyun Cai: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
  2. Fan Feng: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
  3. Haijiao Wang: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
  4. Yanmei Tian: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
  5. Rong Luo: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
  6. Fan Yang: Cipher Gene LLC, Beijing, China.
  7. Xiao Qian: Cipher Gene LLC, Beijing, China.
  8. Zhongjie Zhou: Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, China. ORCID
PMID: 40070083 DOI: 10.1002/jdn.70012

Abstract

INTRODUCTION: O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant disorder associated with KMT2E gene variants. ODLURO syndrome is characterized mainly by developmental delay, intellectual disability and macrocephaly or microcephaly; in some patients, it may manifest as autism or epilepsy.
METHODS: Trio whole-exome sequencing was performed on a female infant with unexplained West syndrome and developmental regression. A de novo splicing variant in the KMT2E gene was identified. The effects of this variant were analysed via a minigene splice assay and in vitro reverse transcription PCR.
RESULTS: The patient presented with spasmodic seizures and developmental delay at 6���months of age. The video electroencephalogram (EEG) displayed hypsarrhythmia. Brain MRI revealed abnormal signals around the lateral ventricles and decreased white matter volume. A novel splicing variant in the KMT2E gene (NM_182931.3: c.1248_1248+9del) was identified in our proband. Sanger sequencing confirmed that the variant was not inherited from her parents. The in vitro minigene assay confirmed that c.1248_1248+9del resulted in exon 12 skipping.
CONCLUSION: To our knowledge, this is the first definite report of ODLURO syndrome with West syndrome as the original manifestation. The deleterious effects of KMT2E c.1248_1248+9del were demonstrated in our proband. Splicing variants in the KMT2E gene are rare, and our study expands the phenotype and genotype of ODLURO syndrome. Additional studies are needed to explore the genotype-phenotype correlations of this disease.

Keywords

KMT2E O'Donnell���Luria���Rodan syndrome genotype���phenotype correlation neurodevelopmental disorder whole���exome sequencing

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Grants

  1. 81801311/National Natural Science Foundation of China Youth Science Foundation Project

MeSH Term

Humans
Female
Phenotype
Infant
Spasms, Infantile
Genotype
Intellectual Disability
Developmental Disabilities
Mutation
RNA Splicing
Autistic Disorder
Epilepsy
Facies
Journal Article Case Reports

Word Cloud

Created with Highcharts 10.0.0syndromeKMT2EODLUROgenevariantdevelopmentalsequencingWestc1248_1248+9delO'Donnell-Luria-Rodandisordervariantsdelaysplicingidentifiedeffectsminigeneassayin vitroprobandconfirmedSplicingINTRODUCTION:autosomaldominantassociatedcharacterizedmainlyintellectualdisabilitymacrocephalymicrocephalypatientsmaymanifestautismepilepsyMETHODS:Triowhole-exomeperformedfemaleinfantunexplainedregressiondenovoanalysedviasplicereversetranscriptionPCRRESULTS:patientpresentedspasmodicseizures6���monthsagevideoelectroencephalogramEEGdisplayedhypsarrhythmiaBrainMRIrevealedabnormalsignalsaroundlateralventriclesdecreasedwhitemattervolumenovelNM_1829313:Sangerinheritedparentsresultedexon12skippingCONCLUSION:knowledgefirstdefinitereportoriginalmanifestationdeleteriousdemonstratedrarestudyexpandsphenotypegenotypeAdditionalstudiesneededexploregenotype-phenotypecorrelationsdiseaseNovelVariantCauseSyndromeSyndrome:ExpansionPhenotypeGenotypeO'Donnell���Luria���Rodangenotype���phenotypecorrelationneurodevelopmentalwhole���exome

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