背景:过氧化物酶体生物发生障碍(PBD)是由PEX基因变异导致的,这些变异会损害过氧化物酶体功能。Zellweger谱系障碍(ZSD)是最严重和最常见的PBD亚型,由于过氧化物酶体参与各种代谢功能而影响多个器官系统。PEX13基因变异是ZSD的罕见原因,全球仅报告21例,中国无一例。
方法:我们描述了一个因PEX13基因变异而生化和分子确认ZSD的婴儿,通过全外显子组测序鉴定并通过Sanger测序验证。随访患者的治疗情况及预后。我们还回顾了以前报道的PEX13变异病例的文献。
结果:患者有严重的低张力,癫痫发作,肝功能障碍,未能茁壮成长,和畸形特征。血清分析显示超长链脂肪酸(VLCFA)水平升高,植酸,和哌啶酸。我们检测到一个新的纯合错义变体c.493G>C(p。Ala165Pro)在PEX13基因(NM_002618.3)中,引起严重的临床表现,遗传自近亲。患者在14个月大时死亡。
结论:我们报告了中国首例因PEX13变异导致的ZSD。我们的发现拓宽了PEX13基因的突变谱,并表明错义变异可导致严重的ZSD表型。这对基因型-表型相关性和遗传咨询有影响。
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.
CONCLUSIONS: 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.