Novel Mutation in ATP6V1A Gene with Infantile Spasms in an Indian Boy

Kadwa, Razia Adam

doi:10.1055/s-0040-1701657

Cited by 4 publications

(1 citation statement)

References 6 publications

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“…ATP6V1A (H + -transporting two-sector ATPase; underexpressed DEP with −2.17 FC) is part of a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signaling pathways. ATP6V1A variants, mainly clustering within the ATP synthase α/β family-nucleotide-binding domain, include early lethal encephalopathies and developmental encephalopathy in epilepsy [ 95 , 96 , 97 ]. Interestingly, several mutants of ATP6V1A , such as the p.Asp100Tyr, are characterized by reduced expression due to increased degradation; these mutations caused a defect in neurite elongation accompanied by loss of excitatory inputs, revealing that altered lysosomal homeostasis markedly affects neurite development and synaptic connectivity [ 95 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomic and Bioinformatic Tools to Identify Potential Hub Proteins in the Audiogenic Seizure-Prone Hamster GASH/Sal

et al. 2023

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The GASH/Sal (Genetic Audiogenic Seizure Hamster, Salamanca) is a model of audiogenic seizures with the epileptogenic focus localized in the inferior colliculus (IC). The sound-induced seizures exhibit a short latency (7–9 s), which implies innate protein disturbances in the IC as a basis for seizure susceptibility and generation. Here, we aim to study the protein profile in the GASH/Sal IC in comparison to controls. Protein samples from the IC were processed for enzymatic digestion and then analyzed by mass spectrometry in Data-Independent Acquisition mode. After identifying the proteins using the UniProt database, we selected those with differential expression and performed ontological analyses, as well as gene-protein interaction studies using bioinformatics tools. We identified 5254 proteins; among them, 184 were differentially expressed proteins (DEPs), with 126 upregulated and 58 downregulated proteins, and 10 of the DEPs directly related to epilepsy. Moreover, 12 and 7 proteins were uniquely found in the GASH/Sal or the control. The results indicated a protein profile alteration in the epileptogenic nucleus that might underlie the inborn occurring audiogenic seizures in the GASH/Sal model. In summary, this study supports the use of bioinformatics methods in proteomics to delve into the relationship between molecular-level protein mechanisms and the pathobiology of rodent models of audiogenic seizures.

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Section: Discussionmentioning

confidence: 99%

Proteomic and Bioinformatic Tools to Identify Potential Hub Proteins in the Audiogenic Seizure-Prone Hamster GASH/Sal

et al. 2023

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Levetiracetam/valproic acid/zonisamide

2020

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Expanding the Spectrum of Autosomal Dominant ATP6V1A-Related Disease: Case Report and Literature Review

Sirchia,

Taietti,

Donesana

et al. 2024

Genes

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Background: Developmental and epileptic encephalopathies (DEE) are a group of disorders often linked to de novo mutations, including those in the ATP6V1A gene. These mutations, particularly dominant gain-of-function (GOF) variants, have been associated with a spectrum of phenotypes, ranging from severe DEE and infantile spasms to milder conditions like autism spectrum disorder and language delays. Methods: We aim to expand ATP6V1A-related disease spectrum by describing a six-year-old boy who presented with a febrile seizure, mild intellectual disability (ID), language delay, acquired microcephaly, and dysmorphic features. Results: Genetic analysis revealed a novel de novo heterozygous pathogenic variant (c.82G>A, p.Val28Met) in the ATP6V1A gene. He did not develop epilepsy, and neuroimaging remained normal over five years of follow-up. Although ATP6V1A mutations have traditionally been linked to severe neurodevelopmental disorders, often with early-onset epilepsy, they may exhibit milder, non-progressive phenotypes, challenging previous assumptions about the severity of ATP6V1A-related conditions. Conclusions: This case expands the known clinical spectrum, illustrating that not all patients with ATP6V1A mutations exhibit severe neurological impairment or epilepsy and underscoring the importance of including this gene in differential diagnoses for developmental delays, especially when febrile seizures or dysmorphic features are present. Broader genotype–phenotype correlations are essential for improving predictive accuracy and guiding clinical management, especially as more cases with mild presentations are identified.

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Novel Mutation in ATP6V1A Gene with Infantile Spasms in an Indian Boy

Cited by 4 publications

References 6 publications

Proteomic and Bioinformatic Tools to Identify Potential Hub Proteins in the Audiogenic Seizure-Prone Hamster GASH/Sal

Proteomic and Bioinformatic Tools to Identify Potential Hub Proteins in the Audiogenic Seizure-Prone Hamster GASH/Sal

Levetiracetam/valproic acid/zonisamide

Expanding the Spectrum of Autosomal Dominant ATP6V1A-Related Disease: Case Report and Literature Review

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