A milder form of NSRP1-associated neurodevelopmental disorder, caused by a missense variant in the nuclear localization signal.
NSRP1
intellectual disability
neurodevelopmental delay
whole‐genome sequencing
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
29 May 2024
29 May 2024
Historique:
revised:
11
04
2024
received:
04
03
2024
accepted:
14
05
2024
medline:
29
5
2024
pubmed:
29
5
2024
entrez:
29
5
2024
Statut:
aheadofprint
Résumé
Nuclear Speckle Splicing Regulator Protein 1 (NSRP1) is a splice factor found in nuclear speckles, which are small membrane-free organelles implicated in epigenetic regulation, chromatin organization, DNA repair, and RNA modification. Bi-allelic loss-of-function variants in NSRP1 have recently been identified in patients suffering from a severe neurodevelopmental disorder, presenting with neurodevelopmental delay, epilepsy, microcephaly, hypotonia, and spastic cerebral palsy. Described patients acquired neither independent walking nor speech and often showed anomalies on cerebral MRI. Here we describe the case of a 14-year-old girl with motor and language delay as well as intellectual disability, who presents an ataxic gait but walks without assistance and speaks in short sentences. Whole-genome sequencing revealed the compound heterozygous NSRP1 variants c.114 + 2T > G and c.1595T > A (p.Val532Glu). Functional validation using HEK293T cells transfected with either wild-type or mutated GFP-tagged Nsrp1 suggests that the Val532Glu variant interferes with the function of the nuclear localization signal, and leads to mislocalization of NSRP1 in the cytosol, thus confirming the pathogenicity of the observed variant. This case helps to expand the phenotypic and genetic spectrum associated with pathogenic NSRP1 variants and indicates that this diagnosis should also be suspected in patients with milder phenotypes.
Identifiants
pubmed: 38808951
doi: 10.1002/ajmg.a.63727
doi:
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
e63727Subventions
Organisme : Belgian Kids'
Organisme : Brussels - Capital Region - Innoviris
Informations de copyright
© 2024 Wiley Periodicals LLC.
Références
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