Scholarlink

Background <p>Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disease chiefly caused by mutations in <i>ETFDH</i> gene. Mutations in the <i>ETFDH</i> gene lead to abnormal structure, impaired function, and increased degradation of ETFDH protein. However, it is not known why approximately 10% of patients carry single heterozygous variants in <i>ETFDH</i>. We speculate that different variation types (e.g., null variants and missense variants) partially account for the phenomenon.</p> Methods <p>In this study, six databases were searched up until December 01, 2024. Studies describing late-onset MADD patients carrying <i>ETFDH</i> variations were included. The analyses focused on the differences in variation types, computational pathogenicity scores of missense variants, and clinical characteristics between patients with biallelic and single heterozygous variations (biallelic group vs heterozygous group).</p> Results <p>Of the initially screened 3638 studies, 30 met the inclusion criteria, including 498 late-onset MADD patients with biallelic variations and 62 with single heterozygous variations&#xa0;in <i>ETFDH</i>. The relative frequency of patients carrying null variants was lower in the biallelic group (21%, 95% CI [16%-27%]) than that in the heterozygous group (34%, 95% CI [23%-48%]) (<i>P</i> = 0.044). Missense variants in the heterozygous group had stronger pathogenicity than those in the biallelic group, as reflected by the computational prediction tools, SIFT, PolyPhen-2 and metaRNN (<i>P</i> &lt; 0.05). Patients carrying biallelic variations had a younger onset age and a higher level of serum creatine kinase at diagnosis (<i>P</i> &lt; 0.05).</p> Conclusions <p>Late-onset MADD patients carrying single heterozygous variations in <i>ETFDH</i> gene have distinct variation profiles and clinical severity compared to those harboring biallelic variations, which highlights the complexity of this disease.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

The difference of variation types between late-onset multiple acyl-CoA dehydrogenase deficiency patients carrying biallelic and single heterozygous variations in ETFDH: a systematic review and meta-analysis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月18日

查看全文
  • Huiqiu Zhang,
  • Jing Ma,
  • Menghan Su,
  • Junsen Zhao,
  • Weisong Duan,
  • Juan Wang,
  • Dan Liu,
  • Junhong Guo,
  • Xueli Chang,
  • Wei Zhang,
  • Rongjuan Zhao

摘要

Background

Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disease chiefly caused by mutations in ETFDH gene. Mutations in the ETFDH gene lead to abnormal structure, impaired function, and increased degradation of ETFDH protein. However, it is not known why approximately 10% of patients carry single heterozygous variants in ETFDH. We speculate that different variation types (e.g., null variants and missense variants) partially account for the phenomenon.

Methods

In this study, six databases were searched up until December 01, 2024. Studies describing late-onset MADD patients carrying ETFDH variations were included. The analyses focused on the differences in variation types, computational pathogenicity scores of missense variants, and clinical characteristics between patients with biallelic and single heterozygous variations (biallelic group vs heterozygous group).

Results

Of the initially screened 3638 studies, 30 met the inclusion criteria, including 498 late-onset MADD patients with biallelic variations and 62 with single heterozygous variations in ETFDH. The relative frequency of patients carrying null variants was lower in the biallelic group (21%, 95% CI [16%-27%]) than that in the heterozygous group (34%, 95% CI [23%-48%]) (P = 0.044). Missense variants in the heterozygous group had stronger pathogenicity than those in the biallelic group, as reflected by the computational prediction tools, SIFT, PolyPhen-2 and metaRNN (P < 0.05). Patients carrying biallelic variations had a younger onset age and a higher level of serum creatine kinase at diagnosis (P < 0.05).

Conclusions

Late-onset MADD patients carrying single heterozygous variations in ETFDH gene have distinct variation profiles and clinical severity compared to those harboring biallelic variations, which highlights the complexity of this disease.