Exploring precision medicine through genome sequencing for patients suspected of rare genetic disorders
Clinical Genetics and Therapeutics
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Primary Categories:
- Clinical Genetics
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Secondary Categories:
- Clinical Genetics
Introduction:
Genome sequencing (GS) has brought diagnosis closer to patients with rare genetic diseases. However, there are still obstacles in the clinical process. This study explores the performance of precision medicine in 901 individuals from 387 families with rare genetic diseases, through precise molecular diagnoses with GS and comprehensive genetic counseling and appropriate management.
Methods:
The study enrolled 901 consecutive patients from 387 non-consanguineous families who were clinically suspected to have a genetic disorder at the 8 hospitals in South Korea from August 2023 to November 2023. GS was performed for the diagnosis and genetic counseling was implemented based on the genetic findings.
Results:
The overall diagnostic rate (DR) with positive results and inconclusive results was 27% (104/387) and 9.0% (35/387), respectively. Thirteen percent (14/104) of diagnosed patients could be only diagnosed by GS as the variant were in the deep intron, small copy number variant, or copy neurtral structural variants not identifiable by exome sequencing or array. The DR varied from 0% to 66.7% depending on the disease categories. In the NDD and dysmorphic and congenital abnormality syndromes that included the most pediatric patients, the DR was 33.7% (33/98, 95% CI: 24.3-43.1%) and 34.9% (15/43, 95% CI: 20.7-49.1%), respectively. The cardiovascular and opthalmologic disorder group that included the most adult patients had a DR of 23.8% (5/21, 95% CI: 5.6-42%) and 18.9% (10/53, 95% CI: 8.4-29.4%), respectively. Secondary findings were identified in 4.7% (18/387) of cases. Clinical intervention and genetic counselling were done in 37.3% (56/150) and 45.3% (68/150) of participants with genomic findings, respectively. Most common clinical intervention was disease surveillance (51.8%), followed by specific medications (26.8%), solid organ transplantation (10.7%), other surgery (3.6%), bone marrow transplantation (5.4%), and family planning (1.8%). Empowerment through genetic counseling significantly increased after counseling, with pre-test K-GCOS score at 88.6±7.5 and post-test scores at 92.1±11.8 (P < 0.007), and satisfaction with genetic counseling was high.
Conclusion:
This study demonstrated the beneficial outcomes of GS for rare diseases, achieved through a team-based process that includes pre-test surveys, systematic technical analysis, clinical assessment/confirmation, and post-test genetic counseling. Specifically, it highlights the importance of clinical implementation of GS and underscores the value of genetic counseling for both primary and secondary findings.
Genome sequencing (GS) has brought diagnosis closer to patients with rare genetic diseases. However, there are still obstacles in the clinical process. This study explores the performance of precision medicine in 901 individuals from 387 families with rare genetic diseases, through precise molecular diagnoses with GS and comprehensive genetic counseling and appropriate management.
Methods:
The study enrolled 901 consecutive patients from 387 non-consanguineous families who were clinically suspected to have a genetic disorder at the 8 hospitals in South Korea from August 2023 to November 2023. GS was performed for the diagnosis and genetic counseling was implemented based on the genetic findings.
Results:
The overall diagnostic rate (DR) with positive results and inconclusive results was 27% (104/387) and 9.0% (35/387), respectively. Thirteen percent (14/104) of diagnosed patients could be only diagnosed by GS as the variant were in the deep intron, small copy number variant, or copy neurtral structural variants not identifiable by exome sequencing or array. The DR varied from 0% to 66.7% depending on the disease categories. In the NDD and dysmorphic and congenital abnormality syndromes that included the most pediatric patients, the DR was 33.7% (33/98, 95% CI: 24.3-43.1%) and 34.9% (15/43, 95% CI: 20.7-49.1%), respectively. The cardiovascular and opthalmologic disorder group that included the most adult patients had a DR of 23.8% (5/21, 95% CI: 5.6-42%) and 18.9% (10/53, 95% CI: 8.4-29.4%), respectively. Secondary findings were identified in 4.7% (18/387) of cases. Clinical intervention and genetic counselling were done in 37.3% (56/150) and 45.3% (68/150) of participants with genomic findings, respectively. Most common clinical intervention was disease surveillance (51.8%), followed by specific medications (26.8%), solid organ transplantation (10.7%), other surgery (3.6%), bone marrow transplantation (5.4%), and family planning (1.8%). Empowerment through genetic counseling significantly increased after counseling, with pre-test K-GCOS score at 88.6±7.5 and post-test scores at 92.1±11.8 (P < 0.007), and satisfaction with genetic counseling was high.
Conclusion:
This study demonstrated the beneficial outcomes of GS for rare diseases, achieved through a team-based process that includes pre-test surveys, systematic technical analysis, clinical assessment/confirmation, and post-test genetic counseling. Specifically, it highlights the importance of clinical implementation of GS and underscores the value of genetic counseling for both primary and secondary findings.