Related Experiment Video
Updated: Sep 27, 2025
09:34
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
34.1K
Heterozygous PNPT1 Variants Cause Spinocerebellar Ataxia Type 25.
Mathieu Barbier1, Melanie Bahlo2,3, Alessandra Pennisi4,5
1Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière, Paris, France.
Annals of Neurology
|April 12, 2022
Summary
Genetic sequencing identified pathogenic variants in the PNPT1 gene as the cause of spinocerebellar ataxia type 25 (SCA25). This discovery links mitochondrial RNA (mtRNA) trafficking defects to ataxia and interferonopathies.
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- Dominant spinocerebellar ataxias (SCAs) exhibit genetic heterogeneity, with some loci lacking identified causal genes.
- The SCA25 locus was previously mapped but its genetic cause remained elusive.
Purpose of the Study:
- To uncover the genetic etiology of the SCA25 locus using next-generation sequencing (NGS).
- To identify the specific gene responsible for dominant spinocerebellar ataxia type 25.
Main Methods:
- Whole-exome and whole-genome sequencing were performed on families linked to SCA25.
- A cohort of 796 ataxia patients with unknown etiology was analyzed using whole exome sequencing data.
Main Results:
- Pathogenic variants in the Polyribonucleotide Nucleotidyltransferase 1 (PNPT1) gene were identified in individuals with SCA25.
- Identified variants included those causing exon skipping and premature stop codons within the S1-domain of PNPT1.
- Affected individuals showed an elevated type I interferon response, linked to abnormal mitochondrial RNA (mtRNA) trafficking.
Conclusions:
- PNPT1 is identified as a novel gene responsible for SCA25.
- The study reveals a biological link between mtRNA trafficking, interferonopathies, and ataxia.
- Findings suggest PNPT1 variants disrupt mtRNA homeostasis, leading to cellular stress and neurological symptoms.
Related Concept Videos
02:26Comparing Copy Number Variations and SNPs
18.0K
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
18.0K
01:05Single Nucleotide Polymorphisms-SNPs
16.1K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
16.1K
02:18Alternative RNA Splicing
21.8K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.8K
01:31Translation
147.7K
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
147.7K
01:11Genetic Lingo
105.7K
Overview
105.7K
02:41Lethal Alleles
15.8K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
15.8K