Novel intragenic deletion within the FXN gene in a patient with typical phenotype of Friedreich ataxia: may be more prevalent than we think?
Biallelic expansion
Deletion
FXN
Friedreich ataxia (FRDA)
Parental testing
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
01 Dec 2023
01 Dec 2023
Historique:
received:
05
12
2022
accepted:
18
11
2023
medline:
4
12
2023
pubmed:
2
12
2023
entrez:
2
12
2023
Statut:
epublish
Résumé
Friedreich ataxia is the most common inherited ataxia in Europe and is mainly caused by biallelic pathogenic expansions of the GAA trinucleotide repeat in intron 1 of the FXN gene that lead to a decrease in frataxin protein levels. Rarely, affected individuals carry either a large intragenic deletion or whole-gene deletion of FXN on one allele and a full-penetrance expanded GAA repeat on the other allele. We report here a patient that presented the typical clinical features of FRDA and genetic analysis of FXN intron 1 led to the assumption that the patient carried the common biallelic expansion. Subsequently, parental sample testing led to the identification of a novel intragenic deletion involving the 5'UTR upstream region and exons 1 and 2 of the FXN gene by MLPA. With this case, we want to raise awareness about the potentially higher prevalence of intragenic deletions and underline the essential role of parental sample testing in providing accurate genetic counselling.
Sections du résumé
BACKGROUND
BACKGROUND
Friedreich ataxia is the most common inherited ataxia in Europe and is mainly caused by biallelic pathogenic expansions of the GAA trinucleotide repeat in intron 1 of the FXN gene that lead to a decrease in frataxin protein levels. Rarely, affected individuals carry either a large intragenic deletion or whole-gene deletion of FXN on one allele and a full-penetrance expanded GAA repeat on the other allele.
CASE PRESENTATION
METHODS
We report here a patient that presented the typical clinical features of FRDA and genetic analysis of FXN intron 1 led to the assumption that the patient carried the common biallelic expansion. Subsequently, parental sample testing led to the identification of a novel intragenic deletion involving the 5'UTR upstream region and exons 1 and 2 of the FXN gene by MLPA.
CONCLUSIONS
CONCLUSIONS
With this case, we want to raise awareness about the potentially higher prevalence of intragenic deletions and underline the essential role of parental sample testing in providing accurate genetic counselling.
Identifiants
pubmed: 38041144
doi: 10.1186/s12920-023-01743-0
pii: 10.1186/s12920-023-01743-0
pmc: PMC10693098
doi:
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
312Informations de copyright
© 2023. The Author(s).
Références
Neuronal Signal. 2018 Nov 02;2(4):NS20180060
pubmed: 32714592
Arch Neurol. 2012 Jul;69(7):912-6
pubmed: 22409940
Eur J Hum Genet. 2004 Nov;12(11):979-82
pubmed: 15340363
J Appl Genet. 2016 Aug;57(3):349-55
pubmed: 26906906
Mol Genet Metab. 2010 Oct-Nov;101(2-3):238-45
pubmed: 20675166
Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12239-43
pubmed: 11035806
J Neurochem. 2013 Aug;126 Suppl 1:11-20
pubmed: 23859338
Science. 1996 Mar 8;271(5254):1423-7
pubmed: 8596916
Ann Neurol. 2016 Mar;79(3):485-95
pubmed: 26704351
Orphanet J Rare Dis. 2014 Nov 30;9:184
pubmed: 25928624
J Mol Diagn. 2004 Nov;6(4):285-9
pubmed: 15507666
Genet Test Mol Biomarkers. 2012 Sep;16(9):1015-8
pubmed: 22691228
Br J Pharmacol. 2014 Apr;171(8):2174-90
pubmed: 24138602
J Neurochem. 2013 Aug;126 Suppl 1:103-17
pubmed: 23859346
Curr Protoc Bioinformatics. 2013;43:11.10.1-11.10.33
pubmed: 25431634
Int J Mol Sci. 2021 Jul 13;22(14):
pubmed: 34299126