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Am J Med Genet A ; 194(1): 59-63, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37698259

RESUMO

Childhood-onset cardiomyopathy is a genetically heterogeneous group of conditions with several genes implicated. Recently, biallelic loss-of-function variants in PPP1R13L have been reported in association with a syndromic form of dilated cardiomyopathy (DCM). In addition, affected children manifest skin and hair abnormalities, cleft lip and palate (CLP), and eye findings. Here, we delineate the condition further by describing the phenotype associated with a homozygous frameshift variant (p.Arg330 ProfsTer76) in PPP1R13L detected in two sibships in a consanguineous family with six affected children. The index case had DCM and wooly hair, two of his siblings had DCM and CLP while three cousins had, in addition, glaucoma. Global developmental delay was observed in one child. All the children, except one, died during early childhood. Whole exome sequencing and whole genome sequencing did not reveal any other plausible variant. We provide further evidence that implicates PPP1R13L in a variable syndromic form of severe childhood-onset DCM and suggests expanding the spectrum of this condition to include glaucoma. Given the variability of the phenotype associated with PPP1R13-related DCM, a thorough evaluation of each case is highly recommended even in the presence of an apparently isolated DCM.


Assuntos
Cardiomiopatia Dilatada , Fenda Labial , Fissura Palatina , Glaucoma , Criança , Humanos , Pré-Escolar , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/genética , Alelos , Fenda Labial/genética , Fissura Palatina/genética , Fenótipo , Glaucoma/genética , Proteínas Repressoras/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética
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