A systematic analysis of genotype-phenotype associations with PLA2G6.
Parkinsonism Relat Disord
; 112: 105477, 2023 Jul.
Article
em En
| MEDLINE
| ID: mdl-37285793
ABSTRACT
BACKGROUND:
PLA2G6-associated neurodegeneration (PLAN) can be categorized into infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (aNAD), neurodegeneration with brain iron accumulation (NBIA), and early-onset parkinsonism (EOP).OBJECTIVES:
To determine the genotype-phenotype association in PLAN.METHODS:
"PLA2G6" or "PARK14" or "phospholipase A2 group VI" or "iPLA2ß" were searched across MEDLINE from June 23, 1997, to March 1, 2023. A total of 391 patients were identified, and 340 patients of them were finally included in the assessment.RESULTS:
The loss of function (LOF) mutation ratios were significantly different (p < 0.001), highest in INAD, followed by NBIA, aNAD, and EOP. Four ensemble scores (i.e., BayesDel, VARITY, ClinPred, and MetaRNN) were assessed to predict the deleteriousness of missense mutations and demonstrated significant differences (p < 0.001). Binary logistic regression analyses demonstrated that LOF mutations were independently associated with brain iron accumulation (p = 0.006) and ataxia (p = 0.025).CONCLUSIONS:
LOF or more deleterious missense mutations are more likely to promote the development of serious phenotype of PLAN, and LOF mutations are independently associated with brain iron accumulation and ataxia.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Distrofias Neuroaxonais
/
Transtornos Parkinsonianos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article