Genetic profiling and diagnostic strategies for patients with ectodermal dysplasias in Korea.
Ectodermal dysplasia
Exome sequencing
Genetic diseases
High-throughput nucleotide sequencing
Inborn
Korea
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
07 Sep 2024
07 Sep 2024
Historique:
received:
06
09
2023
accepted:
21
08
2024
medline:
8
9
2024
pubmed:
8
9
2024
entrez:
7
9
2024
Statut:
epublish
Résumé
Ectodermal dysplasia (ED) is a rare genetic disorder that affects structures derived from the ectodermal germ layer. In this study, we analyzed the genetic profiles of 27 Korean patients with ED. Whole exome sequencing (WES) was performed on 23 patients, and targeted panel sequencing was conducted on the remaining 4 patients. Among the patients in the cohort, 74.1% (20/27) tested positive for ED. Of these positive cases, EDA and EDAR mutations were found in 80% (16/20). Notably, 23.1% (3/13) of EDA-positive cases exhibited copy number variations. Among the 23 patients who underwent WES, we conducted a virtual panel analysis of eight well-known genes, resulting in diagnoses for 56.5% (13/23) of the cases. Additionally, further analysis of approximately 5,000 OMIM genes identified four more cases, increasing the overall positivity rate by approximately 17%. These findings underscore the potential of WES for improving the diagnostic yield of ED. Remarkably, 94.1% of the patients manifesting the complete triad of ED symptoms (hair/skin/dental) displayed detectable EDA/EDAR mutations. In contrast, none of the 7 patients without these three symptoms exhibited EDA/EDAR mutations. When conducting molecular diagnostics for ED, opting for targeted sequencing of EDA/EDAR mutations is advisable for cases with classical symptoms, while WES is deemed an effective strategy for cases in which these symptoms are absent.
Sections du résumé
BACKGROUND
BACKGROUND
Ectodermal dysplasia (ED) is a rare genetic disorder that affects structures derived from the ectodermal germ layer.
RESULTS
RESULTS
In this study, we analyzed the genetic profiles of 27 Korean patients with ED. Whole exome sequencing (WES) was performed on 23 patients, and targeted panel sequencing was conducted on the remaining 4 patients. Among the patients in the cohort, 74.1% (20/27) tested positive for ED. Of these positive cases, EDA and EDAR mutations were found in 80% (16/20). Notably, 23.1% (3/13) of EDA-positive cases exhibited copy number variations. Among the 23 patients who underwent WES, we conducted a virtual panel analysis of eight well-known genes, resulting in diagnoses for 56.5% (13/23) of the cases. Additionally, further analysis of approximately 5,000 OMIM genes identified four more cases, increasing the overall positivity rate by approximately 17%. These findings underscore the potential of WES for improving the diagnostic yield of ED. Remarkably, 94.1% of the patients manifesting the complete triad of ED symptoms (hair/skin/dental) displayed detectable EDA/EDAR mutations. In contrast, none of the 7 patients without these three symptoms exhibited EDA/EDAR mutations.
CONCLUSIONS
CONCLUSIONS
When conducting molecular diagnostics for ED, opting for targeted sequencing of EDA/EDAR mutations is advisable for cases with classical symptoms, while WES is deemed an effective strategy for cases in which these symptoms are absent.
Identifiants
pubmed: 39244550
doi: 10.1186/s13023-024-03331-6
pii: 10.1186/s13023-024-03331-6
doi:
Substances chimiques
Edar Receptor
0
Ectodysplasins
0
EDAR protein, human
0
EDA protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
329Subventions
Organisme : Korea Centers for Disease Control and Prevention
ID : 6500-6534-306, 4860-306-320
Pays : Republic of Korea
Informations de copyright
© 2024. The Author(s).
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