Implementing genomic medicine in clinical practice for adults with undiagnosed rare diseases

Abstract The global burden of undiagnosed diseases, particularly in adults, is rising due to their significant socioeconomic impact. To address this, we enrolled 232 adult probands with undiagnosed conditions, utilizing bioinformatics tools for genetic analysis. Alongside exome and genome sequencing...

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Main Authors: Jong Hyeon Ahn, Jihoon G. Yoon, Jaeso Cho, Seungbok Lee, Sheehyun Kim, Man Jin Kim, Soo Yeon Kim, Soon-Tae Lee, Kon Chu, Sang Kun Lee, Han-Joon Kim, Jinyoung Youn, Ja-Hyun Jang, Jong-Hee Chae, Jangsup Moon, Jin Whan Cho
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:npj Genomic Medicine
Online Access:https://doi.org/10.1038/s41525-024-00449-1
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author Jong Hyeon Ahn
Jihoon G. Yoon
Jaeso Cho
Seungbok Lee
Sheehyun Kim
Man Jin Kim
Soo Yeon Kim
Soon-Tae Lee
Kon Chu
Sang Kun Lee
Han-Joon Kim
Jinyoung Youn
Ja-Hyun Jang
Jong-Hee Chae
Jangsup Moon
Jin Whan Cho
author_facet Jong Hyeon Ahn
Jihoon G. Yoon
Jaeso Cho
Seungbok Lee
Sheehyun Kim
Man Jin Kim
Soo Yeon Kim
Soon-Tae Lee
Kon Chu
Sang Kun Lee
Han-Joon Kim
Jinyoung Youn
Ja-Hyun Jang
Jong-Hee Chae
Jangsup Moon
Jin Whan Cho
author_sort Jong Hyeon Ahn
collection DOAJ
description Abstract The global burden of undiagnosed diseases, particularly in adults, is rising due to their significant socioeconomic impact. To address this, we enrolled 232 adult probands with undiagnosed conditions, utilizing bioinformatics tools for genetic analysis. Alongside exome and genome sequencing, repeat-primed PCR and Cas9-mediated nanopore sequencing were applied to suspected short tandem repeat disorders. Probands were classified into probable genetic (n = 128) or uncertain (n = 104) origins. The study found genetic causes in 66 individuals (28.4%) and non-genetic causes in 12 (5.2%), with a longer diagnostic journey for those in the probable genetic group or with pediatric symptom onset, emphasizing the need for increased efforts in these populations. Genetic diagnoses facilitated effective surveillance, cascade screening, drug repurposing, and pregnancy planning. This study demonstrates that integrating sequencing technologies improves diagnostic accuracy, may shorten the time to diagnosis, and enhances personalized management for adults with undiagnosed diseases.
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publishDate 2024-11-01
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series npj Genomic Medicine
spelling doaj-art-49b5f7d7d62c42b19e87bd0c4acb83082024-12-01T12:38:13ZengNature Portfolionpj Genomic Medicine2056-79442024-11-019111210.1038/s41525-024-00449-1Implementing genomic medicine in clinical practice for adults with undiagnosed rare diseasesJong Hyeon Ahn0Jihoon G. Yoon1Jaeso Cho2Seungbok Lee3Sheehyun Kim4Man Jin Kim5Soo Yeon Kim6Soon-Tae Lee7Kon Chu8Sang Kun Lee9Han-Joon Kim10Jinyoung Youn11Ja-Hyun Jang12Jong-Hee Chae13Jangsup Moon14Jin Whan Cho15Department of Neurology, Samsung Medical Centre, Sungkyunkwan University School of MedicineDepartment of Genomic Medicine, Seoul National University HospitalDepartment of Genomic Medicine, Seoul National University HospitalDepartment of Genomic Medicine, Seoul National University HospitalDepartment of Genomic Medicine, Seoul National University HospitalDepartment of Genomic Medicine, Seoul National University HospitalDepartment of Genomic Medicine, Seoul National University HospitalDepartment of Neurology, Seoul National University HospitalDepartment of Neurology, Seoul National University HospitalDepartment of Neurology, Seoul National University HospitalDepartment of Neurology, Seoul National University HospitalDepartment of Neurology, Samsung Medical Centre, Sungkyunkwan University School of MedicineDepartment of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Genomic Medicine, Seoul National University HospitalDepartment of Genomic Medicine, Seoul National University HospitalDepartment of Neurology, Samsung Medical Centre, Sungkyunkwan University School of MedicineAbstract The global burden of undiagnosed diseases, particularly in adults, is rising due to their significant socioeconomic impact. To address this, we enrolled 232 adult probands with undiagnosed conditions, utilizing bioinformatics tools for genetic analysis. Alongside exome and genome sequencing, repeat-primed PCR and Cas9-mediated nanopore sequencing were applied to suspected short tandem repeat disorders. Probands were classified into probable genetic (n = 128) or uncertain (n = 104) origins. The study found genetic causes in 66 individuals (28.4%) and non-genetic causes in 12 (5.2%), with a longer diagnostic journey for those in the probable genetic group or with pediatric symptom onset, emphasizing the need for increased efforts in these populations. Genetic diagnoses facilitated effective surveillance, cascade screening, drug repurposing, and pregnancy planning. This study demonstrates that integrating sequencing technologies improves diagnostic accuracy, may shorten the time to diagnosis, and enhances personalized management for adults with undiagnosed diseases.https://doi.org/10.1038/s41525-024-00449-1
spellingShingle Jong Hyeon Ahn
Jihoon G. Yoon
Jaeso Cho
Seungbok Lee
Sheehyun Kim
Man Jin Kim
Soo Yeon Kim
Soon-Tae Lee
Kon Chu
Sang Kun Lee
Han-Joon Kim
Jinyoung Youn
Ja-Hyun Jang
Jong-Hee Chae
Jangsup Moon
Jin Whan Cho
Implementing genomic medicine in clinical practice for adults with undiagnosed rare diseases
npj Genomic Medicine
title Implementing genomic medicine in clinical practice for adults with undiagnosed rare diseases
title_full Implementing genomic medicine in clinical practice for adults with undiagnosed rare diseases
title_fullStr Implementing genomic medicine in clinical practice for adults with undiagnosed rare diseases
title_full_unstemmed Implementing genomic medicine in clinical practice for adults with undiagnosed rare diseases
title_short Implementing genomic medicine in clinical practice for adults with undiagnosed rare diseases
title_sort implementing genomic medicine in clinical practice for adults with undiagnosed rare diseases
url https://doi.org/10.1038/s41525-024-00449-1
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