Cargando…

Whole-genome sequencing in clinically diagnosed Charcot–Marie–Tooth disease undiagnosed by whole-exome sequencing

Whole-genome sequencing is the most comprehensive form of next-generation sequencing method. We aimed to assess the additional diagnostic yield of whole-genome sequencing in patients with clinically diagnosed Charcot–Marie–Tooth disease when compared with whole-exome sequencing, which has not been r...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Young-gon, Kwon, Hyemi, Park, Jong-ho, Nam, Soo Hyun, Ha, Changhee, Shin, Sunghwan, Heo, Won Young, Kim, Hye Jin, Chung, Ki Wha, Jang, Ja-Hyun, Kim, Jong-Won, Choi, Byung-Ok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10174204/
https://www.ncbi.nlm.nih.gov/pubmed/37180992
http://dx.doi.org/10.1093/braincomms/fcad139
_version_ 1785039982279262208
author Kim, Young-gon
Kwon, Hyemi
Park, Jong-ho
Nam, Soo Hyun
Ha, Changhee
Shin, Sunghwan
Heo, Won Young
Kim, Hye Jin
Chung, Ki Wha
Jang, Ja-Hyun
Kim, Jong-Won
Choi, Byung-Ok
author_facet Kim, Young-gon
Kwon, Hyemi
Park, Jong-ho
Nam, Soo Hyun
Ha, Changhee
Shin, Sunghwan
Heo, Won Young
Kim, Hye Jin
Chung, Ki Wha
Jang, Ja-Hyun
Kim, Jong-Won
Choi, Byung-Ok
author_sort Kim, Young-gon
collection PubMed
description Whole-genome sequencing is the most comprehensive form of next-generation sequencing method. We aimed to assess the additional diagnostic yield of whole-genome sequencing in patients with clinically diagnosed Charcot–Marie–Tooth disease when compared with whole-exome sequencing, which has not been reported in the literature. Whole-genome sequencing was performed on 72 families whose genetic cause of clinically diagnosed Charcot–Marie–Tooth disease was not revealed after the whole-exome sequencing and 17p12 duplication screening. Among the included families, 14 (19.4%) acquired genetic diagnoses that were compatible with their phenotypes. The most common factor that led to the additional diagnosis in the whole-genome sequencing was genotype-driven analysis (four families, 4/14), in which a wider range of genes, not limited to peripheral neuropathy-related genes, were analysed. Another four families acquired diagnosis due to the inherent advantage of whole-genome sequencing such as better coverage than the whole-exome sequencing (two families, 2/14), structural variants (one family, 1/14) and non-coding variants (one family, 1/14). In conclusion, an evident gain in diagnostic yield was obtained from whole-genome sequencing of the whole-exome sequencing-negative cases. A wide range of genes, not limited to inherited peripheral neuropathy-related genes, should be targeted during whole-genome sequencing.
format Online
Article
Text
id pubmed-10174204
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-101742042023-05-12 Whole-genome sequencing in clinically diagnosed Charcot–Marie–Tooth disease undiagnosed by whole-exome sequencing Kim, Young-gon Kwon, Hyemi Park, Jong-ho Nam, Soo Hyun Ha, Changhee Shin, Sunghwan Heo, Won Young Kim, Hye Jin Chung, Ki Wha Jang, Ja-Hyun Kim, Jong-Won Choi, Byung-Ok Brain Commun Original Article Whole-genome sequencing is the most comprehensive form of next-generation sequencing method. We aimed to assess the additional diagnostic yield of whole-genome sequencing in patients with clinically diagnosed Charcot–Marie–Tooth disease when compared with whole-exome sequencing, which has not been reported in the literature. Whole-genome sequencing was performed on 72 families whose genetic cause of clinically diagnosed Charcot–Marie–Tooth disease was not revealed after the whole-exome sequencing and 17p12 duplication screening. Among the included families, 14 (19.4%) acquired genetic diagnoses that were compatible with their phenotypes. The most common factor that led to the additional diagnosis in the whole-genome sequencing was genotype-driven analysis (four families, 4/14), in which a wider range of genes, not limited to peripheral neuropathy-related genes, were analysed. Another four families acquired diagnosis due to the inherent advantage of whole-genome sequencing such as better coverage than the whole-exome sequencing (two families, 2/14), structural variants (one family, 1/14) and non-coding variants (one family, 1/14). In conclusion, an evident gain in diagnostic yield was obtained from whole-genome sequencing of the whole-exome sequencing-negative cases. A wide range of genes, not limited to inherited peripheral neuropathy-related genes, should be targeted during whole-genome sequencing. Oxford University Press 2023-04-28 /pmc/articles/PMC10174204/ /pubmed/37180992 http://dx.doi.org/10.1093/braincomms/fcad139 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Kim, Young-gon
Kwon, Hyemi
Park, Jong-ho
Nam, Soo Hyun
Ha, Changhee
Shin, Sunghwan
Heo, Won Young
Kim, Hye Jin
Chung, Ki Wha
Jang, Ja-Hyun
Kim, Jong-Won
Choi, Byung-Ok
Whole-genome sequencing in clinically diagnosed Charcot–Marie–Tooth disease undiagnosed by whole-exome sequencing
title Whole-genome sequencing in clinically diagnosed Charcot–Marie–Tooth disease undiagnosed by whole-exome sequencing
title_full Whole-genome sequencing in clinically diagnosed Charcot–Marie–Tooth disease undiagnosed by whole-exome sequencing
title_fullStr Whole-genome sequencing in clinically diagnosed Charcot–Marie–Tooth disease undiagnosed by whole-exome sequencing
title_full_unstemmed Whole-genome sequencing in clinically diagnosed Charcot–Marie–Tooth disease undiagnosed by whole-exome sequencing
title_short Whole-genome sequencing in clinically diagnosed Charcot–Marie–Tooth disease undiagnosed by whole-exome sequencing
title_sort whole-genome sequencing in clinically diagnosed charcot–marie–tooth disease undiagnosed by whole-exome sequencing
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10174204/
https://www.ncbi.nlm.nih.gov/pubmed/37180992
http://dx.doi.org/10.1093/braincomms/fcad139
work_keys_str_mv AT kimyounggon wholegenomesequencinginclinicallydiagnosedcharcotmarietoothdiseaseundiagnosedbywholeexomesequencing
AT kwonhyemi wholegenomesequencinginclinicallydiagnosedcharcotmarietoothdiseaseundiagnosedbywholeexomesequencing
AT parkjongho wholegenomesequencinginclinicallydiagnosedcharcotmarietoothdiseaseundiagnosedbywholeexomesequencing
AT namsoohyun wholegenomesequencinginclinicallydiagnosedcharcotmarietoothdiseaseundiagnosedbywholeexomesequencing
AT hachanghee wholegenomesequencinginclinicallydiagnosedcharcotmarietoothdiseaseundiagnosedbywholeexomesequencing
AT shinsunghwan wholegenomesequencinginclinicallydiagnosedcharcotmarietoothdiseaseundiagnosedbywholeexomesequencing
AT heowonyoung wholegenomesequencinginclinicallydiagnosedcharcotmarietoothdiseaseundiagnosedbywholeexomesequencing
AT kimhyejin wholegenomesequencinginclinicallydiagnosedcharcotmarietoothdiseaseundiagnosedbywholeexomesequencing
AT chungkiwha wholegenomesequencinginclinicallydiagnosedcharcotmarietoothdiseaseundiagnosedbywholeexomesequencing
AT jangjahyun wholegenomesequencinginclinicallydiagnosedcharcotmarietoothdiseaseundiagnosedbywholeexomesequencing
AT kimjongwon wholegenomesequencinginclinicallydiagnosedcharcotmarietoothdiseaseundiagnosedbywholeexomesequencing
AT choibyungok wholegenomesequencinginclinicallydiagnosedcharcotmarietoothdiseaseundiagnosedbywholeexomesequencing