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ORIGINAL RESEARCH article

Front. Neurol.
Sec. Neurogenetics
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1400989
This article is part of the Research Topic Genetics in Rare Neurological Diseases: From Discovery to Targeted Treatment View all 8 articles

Title Novel HEXA Splice Site Mutations in Patient with late atypical onset Tay-Sachs disease: importance of combined NGS and biochemical analysis

Provisionally accepted
Alina Bilyalova Alina Bilyalova 1Elena Shagimardanova Elena Shagimardanova 1,2,3*Airat Bilyalov Airat Bilyalov 1,2*Marina Zaripova Marina Zaripova 1Leyla Shigapova Leyla Shigapova 1Guzel Gazizova Guzel Gazizova 1Pasha Mazin Pasha Mazin 4Ekaterina Zakharova Ekaterina Zakharova 5Oleg Gusev Oleg Gusev 1,3,6
  • 1 Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Tatarstan, Russia
  • 2 A.S.Loginov Moscow Clinical Scientific Centre, Moscow, Moscow Oblast, Russia
  • 3 Other, Moscow, Russia
  • 4 Center for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, Moscow, Russia
  • 5 Research Centre for Medical Genetics, Moscow, Moscow Oblast, Russia
  • 6 School of Medicine, Juntendo University, Bunkyo, Japan

The final, formatted version of the article will be published soon.

    Tay-Sachs disease (TSD) is a rare genetic disorder with diverse clinical manifestations, often leading to underdiagnosis due to symptom similarities with other neurological conditions. We aimed to uncover the genetic underpinnings of late-onset TSD in a 27-year-old patient with progressive neurological symptoms. Whole exome sequencing revealed two hexA gene mutations linked to TSD: a known c.805G>A (p.Gly269Ser) variant and a novel splice site mutation, c.346+2dupT. Clinical assessments, genetic analysis, and functional investigations, including RNA sequencing and enzymatic activity assays, confirmed the novel mutation's pathogenicity. Our findings highlight the efficacy of advanced genomic technologies in diagnosing intricate genetic disorders and emphasize the significance of functional validation for confirming mutation effects. Identifying compound heterozygous mutations in the hexA gene sheds light on Mendelian inheritance patterns. This case underscores the diagnostic challenges posed by overlapping clinical phenotypes and stresses the need for heightened genetic awareness among clinicians. Accurate TSD diagnosis profoundly impacts patients and families, enabling informed genetic counseling and guiding clinical management choices. While treatment options are limited, timely and accurate diagnosis holds promise for future research and interventions. This study showcases the value of a multidisciplinary approach in unraveling the molecular basis of complex genetic diseases and informing clinical decisions. удалено: 1, 34 отформатировано: надстрочные, выделение цветом отформатировано: Шрифт: курсив отформатировано: выделение цветом удалено: gangliosidoses 78 отформатировано: выделение цветом удалено: The adult-onset TSD has strong varyation of age of the 79 disease debut and a heterogeneity of clinical manifestation, resulting

    Keywords: Tay-Sachs Disease, HEXA gene, Next-generation sequencing, Neurology, RNA

    Received: 14 Mar 2024; Accepted: 02 Sep 2024.

    Copyright: © 2024 Bilyalova, Shagimardanova, Bilyalov, Zaripova, Shigapova, Gazizova, Mazin, Zakharova and Gusev. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Elena Shagimardanova, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, 420012, Tatarstan, Russia
    Airat Bilyalov, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, 420012, Tatarstan, Russia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.