Confirming the enzymatic activity and neurodevelopmental trajectory of PYCR1 mutation in one child with autosomal-recessive cutis laxa type 2.
Autosomal recessive cutis laxa type 2B (ARCL2B)
Developmental delay
Enzyme activity
Missense mutation
Pyrroline-5-carboxylate reductase 1 (PYCR1)
Wrinkly skin disorder
Journal
Molecular genetics and genomics : MGG
ISSN: 1617-4623
Titre abrégé: Mol Genet Genomics
Pays: Germany
ID NLM: 101093320
Informations de publication
Date de publication:
22 Aug 2024
22 Aug 2024
Historique:
received:
09
02
2024
accepted:
30
07
2024
medline:
22
8
2024
pubmed:
22
8
2024
entrez:
22
8
2024
Statut:
epublish
Résumé
Autosomal-recessive cutis laxa type 2 (ARCL2) is a rare genetic disorder caused by pyrroline-5-carboxylate reductase 1 (PYCR1) mutations and characterized by loose and sagging skin, typical facial features, intrauterine growth retardation, and developmental delay. To study the effect of PYCR1 mutations on protein function and clinical features, we identified a homozygous missense mutation c.559G > A (p.Ala187Thr) in PYCR1 in a Chinese child with typical clinical features, especially severe developmental delays. The three-dimensional (3D) model showed the modification of the hydrogen bonds produce a misfolding in the mutant PYCR1 protein. Mutagenesis and enzyme assay study revealed decreased activity of the mutant protein in vitro, indicating that this mutation impairs PYCR1 function. Our findings confirmed abnormal enzymatic activity and neurodevelopmental trajectory of this PYCR1 mutation.
Identifiants
pubmed: 39172257
doi: 10.1007/s00438-024-02173-y
pii: 10.1007/s00438-024-02173-y
doi:
Substances chimiques
Pyrroline Carboxylate Reductases
EC 1.5.1.-
delta-1-Pyrroline-5-Carboxylate Reductase
EC 1.5.1.2
Types de publication
Journal Article
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
81Subventions
Organisme : The Beijing Municipal Administration of Hospitals Incubating Program
ID : PX2023049
Organisme : The Beijing Municipal Administration of Hospitals Incubating Program
ID : PX2020056
Organisme : Clinical Testing research fund of the Capital Institute of Pediatrics
ID : CTR005
Informations de copyright
© 2024. The Author(s).
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