Novel phosphopantothenoylcysteine synthetase (PPCS) mutations with prominent neuromuscular features: Expanding the phenotypical spectrum of PPCS-related disorders.
PPCS gene
coenzyme a
dilated cardiomyopathy
pantethine, neonatal necrotizing myopathy
phosphopantothenoylcysteine synthetase
rhabdomyolysis
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:
09 2022
09 2022
Historique:
revised:
17
03
2022
received:
06
01
2022
accepted:
26
03
2022
pubmed:
27
5
2022
medline:
17
8
2022
entrez:
26
5
2022
Statut:
ppublish
Résumé
Biallelic pathogenic variants in phosphopantothenoylcysteine synthetase, PPCS, are a rare cause of a severe early-onset dilated cardiomyopathy with high morbidity and mortality. To date, only five individuals with PPCS-mutations have been reported. Here, we report a female infant who presented in the neonatal period with hypotonia, a necrotizing myopathy with intermittent rhabdomyolysis and other extracardiac manifestations before developing a progressive and ultimately fatal dilated cardiomyopathy. Gene agnostic trio genome sequencing revealed two rare variants in the PPCS [MIM: 609853] in trans, a previously reported pathogenic c.320_334del p. (Pro107_Ala111del) variant, and a c.613-3C>G intronic variant of uncertain significance. Functional studies confirmed the likely pathogenicity of this variant. Our case provides clinical and histopathological evidence for an associated neuromuscular phenotype not previously recognized and expands the evolving phenotypic spectrum of PPCS-related disorders. We also performed a literature search of all previously published cases and summarize the common features.
Identifiants
pubmed: 35616428
doi: 10.1002/ajmg.a.62848
doi:
Types de publication
Case Reports
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2783-2789Subventions
Organisme : Wellcome Trust
ID : 203105/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S005021/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0800674
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
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