ArticleMolecular genetics & genomic medicine2019
Whole genome sequencing reveals novel IGHMBP2 variant leading to unique cryptic splice-site and Charcot-Marie-Tooth phenotype with early onset symptoms.
Article in Molecular genetics & genomic medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Exploring the relationship betweenFrontiers in neuroscience · 2023Pooled it
- A class of deep intronicmedRxiv : the preprint server for health sciences · 2026Article
- Unleashing the Power of Multiomics: Unraveling the Molecular Landscape of Peripheral Neuropathy.Annals of clinical and translational neurology · 2025Review
- Potential ASO-based personalized treatment for Charcot-Marie-Tooth disease type 2S.Molecular therapy. Nucleic acids · 2025Article
- Whole genome sequencing increases the diagnostic rate in Charcot-Marie-Tooth disease.Brain : a journal of neurology · 2024Article
- Association of SORD mutation with autosomal recessive asymmetric distal hereditary motor neuropathy.BMC medical genomics · 2022Article
- Lessons learned: next-generation sequencing applied to undiagnosed genetic diseases.The Journal of clinical investigation · 2022Review
- Decoding disease: from genomes to networks to phenotypes.Nature reviews. Genetics · 2021Review
- Next-Generation Sequencing Technologies and Neurogenetic Diseases.Life (Basel, Switzerland) · 2021Review
- Genetic testing for unexplained perinatal disorders.Current opinion in pediatrics · 2021Review
- Analysis of Pathogenic Pseudoexons Reveals Novel Mechanisms Driving Cryptic Splicing.Frontiers in genetics · 2021Article
- Genetic testing for kidney disease of unknown etiology.Kidney international · 2020Review
- Ocular genetics in the genomics age.American journal of medical genetics. Part C, Seminars in medical genetics · 2020Review
- Current understanding of and emerging treatment options for spinal muscular atrophy with respiratory distress type 1 (SMARD1).Cellular and molecular life sciences : CMLS · 2020Review
- Whole genome sequencing reveals novel IGHMBP2 variant leading to unique cryptic splice-site and Charcot-Marie-Tooth phenotype with early onset symptoms.Molecular genetics & genomic medicine · 2019Article
- RNA-Seq Perspectives to Improve Clinical Diagnosis.Frontiers in genetics · 2019Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
backgroundRare variants (RV) in immunoglobulin mu-binding protein 2 (IGHMBP2) [OMIM 600502] can cause an autosomal recessive type of Charcot-Marie-Tooth (CMT) disease [OMIM 616155], an inherited peripheral neuropathy. Over 40 different genes are associated with CMT, with different possible inheritance patterns. METHODS AND
resultsAn 11-year-old female with motor delays was found to have distal atrophy, weakness, and areflexia without bulbar or sensory findings. Her clinical evaluation was unrevealing. Whole exome sequencing (WES) revealed a maternally inherited IGHMBP2 RV (c.1730T>C) predicted to be pathogenic, but no variant on the other allele was identified. Deletion and duplication analysis was negative. She was referred to the Undiagnosed Disease Network (UDN) for further evaluation. Whole genome sequencing (WGS) confirmed the previously identified IGHMBP2 RV and identified a paternally inherited non-coding IGHMBP2 RV. This was predicted to activate a cryptic splice site perturbing IGHMBP2 splicing. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis was consistent with activation of the cryptic splice site. The abnormal transcript was shown to undergo nonsense-mediated decay (NMD), resulting in halpoinsufficiency.
conclusionThis case demonstrates the deficiencies of WES and traditional molecular analyses and highlights the advantages of utilization of WGS and functional studies.
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