Deep intronic variant in MVK as a cause for mevalonic aciduria initially presenting as non-syndromic retinitis pigmentosa.
MVK
RNA splicing
cryptic exon
deep intronic variant
mevalonate kinase deficiency
retinitis pigmentosa
syndrome
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
revised:
25
07
2022
received:
07
05
2022
accepted:
27
07
2022
pubmed:
3
8
2022
medline:
4
11
2022
entrez:
2
8
2022
Statut:
ppublish
Résumé
Non-syndromic retinitis pigmentosa (NSRP) is a clinically and genetically heterogeneous group of disorders characterized by progressive degeneration of the rod and cone photoreceptors, often leading to blindness. The evolving association of syndromic genes to cause NSRP and the increasing role of intronic variants in explaining missing heritability in genetic disorders present challenges in establishing conclusive clinical and genetic diagnoses. This study sought to identify and validate the causative genetic variant(s) in a 13-year-old male initially diagnosed with NSRP. Genome sequencing identified a pathogenic missense variant in MVK [NM_000431.3:c.803T>C (p.Ile268Thr)], in trans with a novel intronic variant predicted to create a new donor splice site (c.768+71C>A). Proband cDNA analysis confirmed the inclusion of the first 68 base pairs of intron 8 that resulted in a frameshift in MVK (r.768_769ins[768+1_768+68]) and significantly reduced the expression of reference transcript (17.6%). Patient re-phenotyping revealed ataxia, cerebellar atrophy, elevated urinary mevalonate and LTE
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
524-529Informations de copyright
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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