RESUMO
OBJECTIVE: To explore the genetic etiology for a newborn with corneal opacity. METHODS: The neonate and her parents were subjected to routine G-banding chromosomal karyotyping analysis. Copy number variation (CNV) was analyzed with low-coverage whole-genome sequencing (WGS) and single nucleotide polymorphism microarray (SNP array). RESULTS: No karyotypic abnormality was found in the newborn and her parents. Low-coverage WGS has identified a de novo 5.5 Mb microdeletion at chromosome 8q21.11-q21.13 in the neonate, which encompassed the ZFHX4 and PEX2 genes. The result was confirmed by SNP array-based CNV analysis. CONCLUSION: The newborn was diagnosed with chromosome 8q21.11 deletion syndrome. ZFHX4 may be one of the key genes underlying this syndrome.
Assuntos
Variações do Número de Cópias de DNA , Testes Genéticos , Monossomia/genética , Bandeamento Cromossômico , Cromossomos Humanos Par 8/genética , Feminino , Proteínas de Homeodomínio/genética , Humanos , Recém-Nascido , Cariotipagem , Fator 2 da Biogênese de Peroxissomos/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genéticaRESUMO
OBJECTIVE@#To explore the genetic etiology for a newborn with corneal opacity.@*METHODS@#The neonate and her parents were subjected to routine G-banding chromosomal karyotyping analysis. Copy number variation (CNV) was analyzed with low-coverage whole-genome sequencing (WGS) and single nucleotide polymorphism microarray (SNP array).@*RESULTS@#No karyotypic abnormality was found in the newborn and her parents. Low-coverage WGS has identified a de novo 5.5 Mb microdeletion at chromosome 8q21.11-q21.13 in the neonate, which encompassed the ZFHX4 and PEX2 genes. The result was confirmed by SNP array-based CNV analysis.@*CONCLUSION@#The newborn was diagnosed with chromosome 8q21.11 deletion syndrome. ZFHX4 may be one of the key genes underlying this syndrome.
Assuntos
Feminino , Humanos , Recém-Nascido , Bandeamento Cromossômico , Cromossomos Humanos Par 8/genética , Variações do Número de Cópias de DNA , Testes Genéticos , Proteínas de Homeodomínio/genética , Cariotipagem , Monossomia/genética , Fator 2 da Biogênese de Peroxissomos/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genéticaRESUMO
The regulation of organelle abundance is critical for cell function and survival; however, the mechanisms responsible are not fully understood. In this study, we characterize a role of the deubiquitinating enzyme USP30 in peroxisome maintenance. Peroxisomes are highly dynamic, changing in abundance in response to metabolic stress. In our recent study identifying the role of USP30 in mitophagy, we observed USP30 to be localized to punctate structures resembling peroxisomes. We report here that USP30, best known as a mitophagy regulator, is also necessary for regulating pexophagy, the selective autophagic degradation of peroxisomes. We find that overexpressing USP30 prevents pexophagy during amino acid starvation, and its depletion results in pexophagy induction under basal conditions. We demonstrate that USP30 prevents pexophagy by counteracting the action of the peroxisomal E3 ubiquitin ligase PEX2. Finally, we show that USP30 can rescue the peroxisome loss observed in some disease-causing peroxisome mutations, pointing to a potential therapeutic target.
