Severe Zellweger spectrum disorder due to a novel missense variant in the PEX13 gene: A case report and the literature review.

Autor: Su L; Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, P. R. China., Peng MZ; Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, P. R. China., Chen XD; Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, P. R. China., Wu S; School of Pediatrics, Guangzhou Medical University, Guangzhou, P. R. China., Liu L; Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, P. R. China.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2024 Jan; Vol. 12 (1), pp. e2315. Date of Electronic Publication: 2023 Nov 14.
DOI: 10.1002/mgg3.2315
Abstrakt: Background: Peroxisome biogenesis disorders (PBDs) are caused by variants in PEX genes that impair peroxisome function. Zellweger spectrum disorders (ZSDs) are the most severe and common subtype of PBDs, affecting multiple organ systems due to peroxisomal involvement in various metabolic functions. PEX13 gene variants are rare causes of ZSDs, with only 21 cases reported worldwide and none in China.
Methods: We describe an infant with biochemically and molecularly confirmed ZSDs due to variants in the PEX13 gene, identified by whole exome sequencing and validated by Sanger sequencing. The patient's treatment and prognosis were followed up. We also reviewed the literature on previously reported cases with PEX13 variants.
Results: The patient had severe hypotonia, seizures, hepatic dysfunction, failure to thrive, and dysmorphic features. Serum analysis revealed elevated levels of very long-chain fatty acids (VLCFA), phytanic acid, and pipecolic acid. We detected a novel homozygous missense variant c.493G>C (p. Ala165Pro) in the PEX13 gene (NM_002618.3), which caused severe clinical manifestations and was inherited from the consanguineous parents. The patient died at the age of 14 months.
Conclusion: We report the first case of ZSDs due to the PEX13 variant in China. Our findings broaden the mutational spectrum of the PEX13 gene and indicate that missense variants can lead to severe ZSDs phenotypes, which has implications for genotype-phenotype correlations and genetic counseling.
(© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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