Confirming the enzymatic activity and neurodevelopmental trajectory of PYCR1 mutation in one child with autosomal-recessive cutis laxa type 2.

Autor: Shangguan S; Department of Medical Genetics, Capital Institute of Pediatrics, Yabao Road, Chaoyang District, Beijing, 100020, China., Zhang X; Department of Children's Nutrition Research Center, Affiliated Children's Hospital of Capital Institute of Pediatrics, Yabao Road, Chaoyang District, Beijing, 100020, China., Ge Y; Department of Medical Genetics, Capital Institute of Pediatrics, Yabao Road, Chaoyang District, Beijing, 100020, China., Han Y; Department of Neurology, Affiliated Children's hospital of Capital Institute of Pediatrics, Beijing, China., Xiao L; Department of Children's Nutrition Research Center, Affiliated Children's Hospital of Capital Institute of Pediatrics, Yabao Road, Chaoyang District, Beijing, 100020, China., Zhang Y; Department of Laboratory Center, Capital Institute of Pediatrics, Beijing, China., Xie H; Department of Medical Genetics, Capital Institute of Pediatrics, Yabao Road, Chaoyang District, Beijing, 100020, China., Chen X; Department of Medical Genetics, Capital Institute of Pediatrics, Yabao Road, Chaoyang District, Beijing, 100020, China. xiaolichen@pumc.edu.cn., Wang X; Department of Children's Nutrition Research Center, Affiliated Children's Hospital of Capital Institute of Pediatrics, Yabao Road, Chaoyang District, Beijing, 100020, China. yanziskyv@126.com.
Jazyk: angličtina
Zdroj: Molecular genetics and genomics : MGG [Mol Genet Genomics] 2024 Aug 22; Vol. 299 (1), pp. 81. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1007/s00438-024-02173-y
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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