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Discovery of a Novel Shared Variant Among RTEL1 Gene and RTEL1-TNFRSF6B lncRNA at Chromosome 20q13.33 in Familial Progressive Myoclonus Epilepsy.
Chaudhari, Sima; Acharya, Lavanya Prakash; Jasti, Dushyanth Babu; Ware, Akshay Pramod; Gorthi, Sankar Prasad; Satyamoorthy, Kapaettu.
Afiliación
  • Chaudhari S; Department of Cell and Molecular Biology Manipal School of Life Sciences Manipal Academy of Higher Education 576104, Manipal, Karnataka, India.
  • Acharya LP; Department of Cell and Molecular Biology Manipal School of Life Sciences Manipal Academy of Higher Education 576104, Manipal, Karnataka, India.
  • Jasti DB; Department of Neurology Kasturba Medical College 576104, Manipal, Karnataka, India.
  • Ware AP; Department of Bioinformatics Manipal School of Life Sciences Manipal Academy of Higher Education 576104, Manipal, Karnataka, India.
  • Gorthi SP; Department of Neurology Kasturba Medical College 576104, Manipal, Karnataka, India.
  • Satyamoorthy K; Department of Neurology Bharati Hospital and Research Center Bharati Vidyapeeth (Deemed to Be University) Medical College and Hospital, Dhankawadi 411043, Pune, Maharashtra, India.
Int J Genomics ; 2024: 7518528, 2024.
Article en En | MEDLINE | ID: mdl-39156922
ABSTRACT

Background:

Progressive myoclonus epilepsy (PME) is a neurodegenerative disorder marked by recurrent seizures and progressive myoclonus. To date, based on the phenotypes and causal genes, more than 40 subtypes of PMEs have been identified, and more remain to be characterized. Our study is aimed at identifying the aberrant gene(s) possibly associated with PMEs in two siblings born to asymptomatic parents, in the absence of known genetic mutations.

Methods:

Clinical assessments and molecular analyses, such as the repeat expansion test for CSTB; SCA1, 2, 3, 6, and 7; whole exome sequencing (WES); and mitochondrial genome sequencing coupled with computational analysis, were performed.

Results:

A family-based segregation analysis of WES data was performed to identify novel genes associated with PMEs. The potassium channel, KCNH8 [c.298T>C; (p.Tyr100His)], a DNA repair gene, regulator of telomere elongation helicase 1 (RTEL1) [c.691G>T; (p.Asp231Tyr)] and long noncoding RNA, RTEL1-TNFRSF6B [chr2062298898_G>T; NR_037882.1, hg19] were among the candidate genes that were found to be associated with PMEs. These homozygous variations in siblings belong to genes with a loss-of-function intolerant (pLI) score of ≤ 0.86, expected to be detrimental by multiple computational analyses, and were heterozygous in parents. Additionally, computational analysis and the expression of RTEL1 and RTEL1-TNFRSF6B revealed that RTEL1-TNFRSF6B may modulate RTEL1 via hsa-miR-3529-3p. In the patient with the severe phenotype, a further deleterious mutation in SLC22A17 was identified. No de novo variants specific to these probands were identified in the mitochondrial genome.

Conclusions:

Our study is the first to report variants in KCNH8, RTEL1, and RTEL1-TNFRSF6B among PME cases. These genes when characterized fully may shed light on pathogenicity and have the potential to be used in the diagnosis of PME.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Int J Genomics Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Int J Genomics Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos