一个新的 PEX6 基因 10 号内含子剪接变异与中国一名新生儿的 Zellweger 综合征相关。
A novel splice variant in intron 10 of PEX6 is associated with Zellweger Syndrome in a Chinese neonate.
机构信息
School of Medicine, Department of Medicine, Wuhan University of Science and Technology, Wuhan 430081, China; Division of Neonatology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430010, China.
Department of Rehabilitation Medicine, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430010, China.
出版信息
Gene. 2024 Nov 30;928:148767. doi: 10.1016/j.gene.2024.148767. Epub 2024 Jul 14.
BACKGROUND
Zellweger Syndrome (ZS), or cerebrohepatorenal syndrome, is a rare disorder due to PEX gene mutations affecting peroxisome function. While PEX6 coding mutations are known to cause ZS, the impact of noncoding mutations is less clear.
METHODS
A Chinese neonate and his family were subjected to whole exome sequencing (WES) and bioinformatics to assess variant pathogenicity. A minigene assay was also performed for detailed splicing variant analysis.
RESULTS
WES identified compound heterozygous PEX6 variants: c.315G>A (p. Trp105Ter) and c.2095-3 T>G. Minigene assays indicated that the latter variant led to abnormal mRNA splicing and the loss of exon 11 in PEX6 expression, potentially causing nonsense-mediated mRNA decay (NMD) or truncated protein structure.
CONCLUSION
The study suggests that PEX6: c.2095-3 T>G might be a genetic contributor to the patient's condition, broadening the known mutation spectrum of PEX6. These insights lay groundwork for potential gene therapy for such variants.
背景
Zellweger 综合征（ZS），又称脑肝肾综合征，是一种罕见的疾病，由于 PEX 基因突变影响过氧化物酶体功能所致。虽然 PEX6 编码突变已知会导致 ZS，但非编码突变的影响尚不清楚。
方法
对一名中国新生儿及其家系进行全外显子组测序（WES）和生物信息学分析，以评估变异的致病性。还进行了小基因检测，以进行详细的剪接变体分析。
结果
WES 鉴定出 PEX6 的复合杂合变异：c.315G>A（p.Trp105Ter）和 c.2095-3T>G。小基因检测表明，后者变异导致 PEX6 表达中的异常 mRNA 剪接和外显子 11 的缺失，可能导致无义介导的 mRNA 降解（NMD）或截短的蛋白结构。
结论
该研究表明，PEX6:c.2095-3T>G 可能是该患者疾病的遗传因素，拓宽了 PEX6 已知的突变谱。这些见解为针对此类变体的潜在基因治疗奠定了基础。
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