Recently, the internationally renowned journal JAMA Pediatrics (IF: 26.1) published a systematic study on the molecular diagnostic rate of patients with dwarfism by a research team in the form of an original monograph. The results of the study showed that the overall diagnostic rate of dwarfism was 27.1% by exome sequencing and 13.6% by chromosome microarray analysis. This is the first international comprehensive statistical analysis of the molecular diagnostic rate of a dwarfism cohort. The results of the study provide high-level clinical evidence for the adoption of exome sequencing and chromosome microarray analysis as diagnostic tools for patients with dwarfism, and have important clinical significance and scientific value.
Dwarfism, with a prevalence between 20/100,000 and 25/100,000, is most common in males. The main manifestations of the disease are slow growth and skeletal underdevelopment, which may be accompanied by underdevelopment of sex organs or lack of secondary sexual characteristics, etc. Early detection, early diagnosis, and early intervention are the principles of treatment for dwarfism. In recent years, exome sequencing and chromosome microarray analysis have been widely used in the field of molecular diagnosis of patients with dwarfism, but there is a lack of clear reports on the diagnostic rate of this disease.
The team searched PubMed, Embase, and Web of Science using relevant keywords to identify studies that included 10 or more patients who had undergone exome sequencing or chromosome microarray analysis as a diagnostic tool, and selected 20 of the 5,222 eligible studies for subsequent analysis.
The team extracted relevant information from each study and used proportional meta-analysis to comb through the data to obtain overall diagnostic rates for exome sequencing and chromosome microarray analysis. The results showed that in the final selection of 10 exome sequencing cohorts (totaling 1,350 individuals) and 14 chromosome microarray analysis cohorts (totaling 1,070 individuals), the overall diagnostic rate for exome sequencing was 27.1% (95% CI, 18.1%-37.2%), and the overall diagnostic rate for chromosome microarray analysis was 13.6% (95% CI, 9.2%-18.7%) .
The team also performed a subgroup analysis of the exome sequencing cohort. The study found that the diagnostic rate of using exome sequencing technology for the first step of a dwarfism diagnosis was slightly higher than using it for the final step, which suggests that physicians should use exome sequencing technology for diagnosis earlier. In addition, the diagnostic rate using exome sequencing technology did not significantly increase over time and with the increase in the level of technology, and the investigators hypothesized that although the sensitivity of genomic technology continues to increase and knowledge of the causative genes and copy number variants continues to increase, the popularity of the technology's use has been accompanied by the inclusion of patients with mild phenotypes who are not genetically predisposed to the disease, which has led to a decrease in the diagnostic rate.
This study provides high-level clinical evidence for the application of exome sequencing and chromosome microarray analysis as diagnostic tools for patients with dwarfism. With the advancement of sequencing technology and the level of data interpretation, the integration of the above genetic testing tools into a comprehensive diagnostic system for dwarfism will allow patients to receive more timely and precise diagnosis and treatment, thus improving their quality of life. The article was selected as an Editor's Choice in the current issue of JAMA Pediatrics, and the editorial boards of the journal from Harvard Children's Hospital Boston, Harvard Health Research Institute, and Harvard Medical School issued a special Editorial comment on the study, “These data provide further support for the use of whole genome testing as the preferred test for patients suspected of having rare genetic disorders. method.”
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