دورية أكاديمية
Primary carnitine deficiency: Estimation of prevalence in Chinese population and insights into newborn screening
| العنوان: | Primary carnitine deficiency: Estimation of prevalence in Chinese population and insights into newborn screening |
|---|---|
| المؤلفون: | Xiaoshan Ji, Yanzhuang Ge, Qi Ni, Suhua Xu, Zhongmeng Xiong, Lin Yang, Liyuan Hu, Yun Cao, Yulan Lu, Qiufen Wei, Wenqing Kang, Deyi Zhuang, Wenhao Zhou, Xinran Dong |
| المصدر: | Frontiers in Genetics, Vol 14 (2023) |
| بيانات النشر: | Frontiers Media S.A., 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Genetics |
| مصطلحات موضوعية: | primary carnitine deficiency, SLC22A5, prevalence estimation, newborn screening, genotype–phenotype analysis, Genetics, QH426-470 |
| الوصف: | Primary carnitine deficiency (PCD) caused by pathogenic variants in the solute carrier family 22 member 5 (SLC22A5) gene is a rare autosomal recessive disease that results in defective fatty acid oxidation. PCD can be detected through tandem mass spectrometry (MS/MS), but transplacental transport of free carnitine from mothers may cause false negatives or positives during newborn screening (NBS). This study aimed to analyze the genetic characteristics of SLC22A5 and estimate the prevalence of PCD in the Chinese population, providing useful information for NBS and genetic counseling. We manually curated SLC22A5 pathogenic or likely pathogenic (P/LP) variants according to the American College of Medical Genetics and Genomics (ACMG) guidelines and identified 128 P/LP variants. Based on the China Neonatal Genomes Project (CNGP), the estimated PCD prevalence was 1:17,456, which was higher than that in other populations. The genotype–phenotype association analysis showed that patients carrying homozygous c.760C>T and c.844C>T were more likely to present cardiomyopathy, whereas those carrying homozygous c.1400C>G were more likely to be asymptomatic (all p-values < 0.05). We found that there was no significant difference in initial C0 concentrations between patients and carriers, but there was a significant difference in the second-tier screening of C0 concentration between them (p-value < 0.05). We established a cost-effective variant panel containing 10 high-frequency sites and developed a screening algorithm incorporating gene panels with MS/MS, which could rescue one more patient who was undetected from MS/MS. In conclusion, the prevalence of PCD in the Chinese population is relatively high. The combination of conventional NBS with genetic sequencing is suggested for early diagnosis of PCD. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1664-8021 93262620 |
| Relation: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1304458/full; https://doaj.org/toc/1664-8021 |
| DOI: | 10.3389/fgene.2023.1304458 |
| URL الوصول: | https://doaj.org/article/5f3c68adea68453ea7eb5ba93262620c |
| رقم الأكسشن: | edsdoj.5f3c68adea68453ea7eb5ba93262620c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 16648021 93262620 |
|---|---|
| DOI: | 10.3389/fgene.2023.1304458 |