PDF(Pubmed)
Abstract：
UNASSIGNED: The context was designed to optimize the diagnostic utility of clinically focused exome sequencing (CFES) and shorten the diagnostic odyssey among pediatric patients suspected of monogenic disorders (MDs).
UNASSIGNED: Here, we retrospectively analyzed the clinical notes of 372 patients from different areas in the Jiangxi province that were referred for a diagnostic CFES and analysis from June 2018 to March 2022 with symptoms suggestive of MDs. In our study, preliminary tests using the proband-only clinical exome sequencing as a cost-effective first-tier diagnostic test for pediatric patients with unidentified MDs, supplemented by family segregation studies for targeted variants when indicated.
UNASSIGNED: Probands with confirmed diagnostic (CD) or likely diagnostic (LD) genetic influences accounted for 12% of all cases, whereas those with an uncertain diagnosis accounted for 48%. We also found that systemic primary carnitine deficiency (CDSP) (SLC22A5 gene) and phenylketonuria (PAH gene) were relatively more prevalent, and these patients with CDSP had the most frequent c.1400C > G variant (p.S467C) and c.51C > G variant (p. F17L) in this study. In addition, statistical analysis revealed that the estimates of diagnostic yields varied across certain phenotypic features of patients, and patients with specific phenotypic traits tended to benefit more from CFES.
UNASSIGNED: The CFES may be a first-line genetic test for diagnosing young children with suspected genetic conditions, as it validates the identification of molecular genetics alterations and facilitates comprehensive medical management. Moreover, we found that infants exhibiting metabolism/homeostasis abnormalities, craniofacial /otolaryngology/ ophthalmologic abnormalities, and/or the integument were significantly more likely to receive a genetic diagnosis via CFES than infants without such features. However, due to the current study\'s low diagnostic yield and inherent limitations, high-quality clinical studies with larger sample sizes are still needed to provide more likely results and confirm our findings.
UNASSIGNED: Here, we retrospectively analyzed the clinical notes of 372 patients from different areas in the Jiangxi province that were referred for a diagnostic CFES and analysis from June 2018 to March 2022 with symptoms suggestive of MDs. In our study, preliminary tests using the proband-only clinical exome sequencing as a cost-effective first-tier diagnostic test for pediatric patients with unidentified MDs, supplemented by family segregation studies for targeted variants when indicated.
UNASSIGNED: Probands with confirmed diagnostic (CD) or likely diagnostic (LD) genetic influences accounted for 12% of all cases, whereas those with an uncertain diagnosis accounted for 48%. We also found that systemic primary carnitine deficiency (CDSP) (SLC22A5 gene) and phenylketonuria (PAH gene) were relatively more prevalent, and these patients with CDSP had the most frequent c.1400C > G variant (p.S467C) and c.51C > G variant (p. F17L) in this study. In addition, statistical analysis revealed that the estimates of diagnostic yields varied across certain phenotypic features of patients, and patients with specific phenotypic traits tended to benefit more from CFES.
UNASSIGNED: The CFES may be a first-line genetic test for diagnosing young children with suspected genetic conditions, as it validates the identification of molecular genetics alterations and facilitates comprehensive medical management. Moreover, we found that infants exhibiting metabolism/homeostasis abnormalities, craniofacial /otolaryngology/ ophthalmologic abnormalities, and/or the integument were significantly more likely to receive a genetic diagnosis via CFES than infants without such features. However, due to the current study\'s low diagnostic yield and inherent limitations, high-quality clinical studies with larger sample sizes are still needed to provide more likely results and confirm our findings.
摘要：
UNASSIGNED：本文旨在优化临床聚焦外显子组测序（CFES）的诊断效用，并缩短疑似单基因疾病（MD）的儿科患者的诊断时间。
未经评估：这里，我们回顾性分析了2018年6月至2022年3月期间江西省不同地区372例患者的临床记录,这些患者接受CFES诊断和分析,症状提示为MD.在我们的研究中,使用先证者临床外显子组测序作为具有成本效益的第一层诊断测试的初步测试，用于患有未识别的MDs的儿科患者，在指示时，通过针对目标变体的家族隔离研究进行补充。
未经证实：具有确诊（CD）或可能诊断（LD）遗传影响的先兆占所有病例的12％，而诊断不确定的占48%。我们还发现系统性原发性肉碱缺乏症（CDSP）（SLC22A5基因）和苯丙酮尿症（PAH基因）相对更普遍，这些CDSP患者的c.1400C>G变异最常见（p。S467C）和c.51C>G变体（p。F17L)在这项研究中。此外,统计分析显示，诊断结果的估计因患者的某些表型特征而异，具有特定表型性状的患者倾向于从CFES中受益更多。
UNASSIGNED：CFES可能是诊断有可疑遗传状况的幼儿的一线遗传测试，因为它验证了分子遗传学改变的识别，并促进了全面的医疗管理。此外，我们发现表现出代谢/稳态异常的婴儿，颅面/耳鼻喉科/眼科异常，与没有此类特征的婴儿相比,和/或受孕者更有可能通过CFES接受基因诊断.然而,由于目前研究的低诊断率和固有的局限性，仍然需要具有更大样本量的高质量临床研究来提供更可能的结果并证实我们的发现.
未经评估：这里，我们回顾性分析了2018年6月至2022年3月期间江西省不同地区372例患者的临床记录,这些患者接受CFES诊断和分析,症状提示为MD.在我们的研究中,使用先证者临床外显子组测序作为具有成本效益的第一层诊断测试的初步测试，用于患有未识别的MDs的儿科患者，在指示时，通过针对目标变体的家族隔离研究进行补充。
未经证实：具有确诊（CD）或可能诊断（LD）遗传影响的先兆占所有病例的12％，而诊断不确定的占48%。我们还发现系统性原发性肉碱缺乏症（CDSP）（SLC22A5基因）和苯丙酮尿症（PAH基因）相对更普遍，这些CDSP患者的c.1400C>G变异最常见（p。S467C）和c.51C>G变体（p。F17L)在这项研究中。此外,统计分析显示，诊断结果的估计因患者的某些表型特征而异，具有特定表型性状的患者倾向于从CFES中受益更多。
UNASSIGNED：CFES可能是诊断有可疑遗传状况的幼儿的一线遗传测试，因为它验证了分子遗传学改变的识别，并促进了全面的医疗管理。此外，我们发现表现出代谢/稳态异常的婴儿，颅面/耳鼻喉科/眼科异常，与没有此类特征的婴儿相比,和/或受孕者更有可能通过CFES接受基因诊断.然而,由于目前研究的低诊断率和固有的局限性，仍然需要具有更大样本量的高质量临床研究来提供更可能的结果并证实我们的发现.
