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Article: Delineation of molecular findings by whole-exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population

TitleDelineation of molecular findings by whole-exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population
Authors
KeywordsMitochondrial disease
Paediatrics
Whole-exome sequencing
Issue Date2020
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.humgenomics.com
Citation
Human Genomics, 2020, v. 14, p. article no. 28 How to Cite?
AbstractBackground Mitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed for our paediatric-onset MD cohort of a Southern Chinese origin, with the aim of identifying key disease-causing variants in the Chinese patients with MDs. Methods We recruited Chinese patients who had paediatric-onset MDs and a minimum mitochondrial disease criteria (MDC) score of 3. Patients with positive target gene or mitochondrial DNA sequencing results were excluded. WES was performed, variants with population frequency ≤ 1% were analysed for pathogenicity on the basis of the American College of Medical Genetics and Genomics guidelines. Results Sixty-six patients with pre-biopsy MDC scores of 3–8 were recruited. The overall diagnostic yield was 35% (23/66). Eleven patients (17%) were found to have mutations in MD-related genes, with COQ4 having the highest mutation rate owing to the Chinese-specific founder mutation (4/66, 6%). Twelve patients (12/66, 18%) had mutations in non-MD-related genes: ATP1A3 (n = 3, two were siblings), ALDH5A1, ARX, FA2H, KCNT1, LDHD, NEFL, NKX2-2, TBCK, and WAC. Conclusions We confirmed that the COQ4:c.370G>A, p.(Gly124Ser) variant, was a founder mutation among the Southern Chinese population. Screening for this mutation should therefore be considered while diagnosing Chinese patients suspected to have MDs. Furthermore, WES has proven to be useful in detecting variants in patients suspected to have MDs because it helps to obtain an unbiased and precise genetic diagnosis for these diseases, which are genetically heterogeneous.
Persistent Identifierhttp://hdl.handle.net/10722/287286
ISSN
2019 Impact Factor: 3.351
2015 SCImago Journal Rankings: 1.632
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorTSANG, MHY-
dc.contributor.authorKwong, AKY-
dc.contributor.authorChan, KLS-
dc.contributor.authorFung, JLF-
dc.contributor.authorYU, MHC-
dc.contributor.authorMak, CCY-
dc.contributor.authorYeung, KS-
dc.contributor.authorRodenburg, RJT-
dc.contributor.authorSmeitink, JAM-
dc.contributor.authorChan, R-
dc.contributor.authorTsoi, T-
dc.contributor.authorHui, J-
dc.contributor.authorWong, SSN-
dc.contributor.authorTai, SM-
dc.contributor.authorChan, VCM-
dc.contributor.authorMa, CK-
dc.contributor.authorFung, STH-
dc.contributor.authorWu, SP-
dc.contributor.authorChak, WK-
dc.contributor.authorChung, BHY-
dc.contributor.authorFung, CW-
dc.date.accessioned2020-09-22T02:58:41Z-
dc.date.available2020-09-22T02:58:41Z-
dc.date.issued2020-
dc.identifier.citationHuman Genomics, 2020, v. 14, p. article no. 28-
dc.identifier.issn1473-9542-
dc.identifier.urihttp://hdl.handle.net/10722/287286-
dc.description.abstractBackground Mitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed for our paediatric-onset MD cohort of a Southern Chinese origin, with the aim of identifying key disease-causing variants in the Chinese patients with MDs. Methods We recruited Chinese patients who had paediatric-onset MDs and a minimum mitochondrial disease criteria (MDC) score of 3. Patients with positive target gene or mitochondrial DNA sequencing results were excluded. WES was performed, variants with population frequency ≤ 1% were analysed for pathogenicity on the basis of the American College of Medical Genetics and Genomics guidelines. Results Sixty-six patients with pre-biopsy MDC scores of 3–8 were recruited. The overall diagnostic yield was 35% (23/66). Eleven patients (17%) were found to have mutations in MD-related genes, with COQ4 having the highest mutation rate owing to the Chinese-specific founder mutation (4/66, 6%). Twelve patients (12/66, 18%) had mutations in non-MD-related genes: ATP1A3 (n = 3, two were siblings), ALDH5A1, ARX, FA2H, KCNT1, LDHD, NEFL, NKX2-2, TBCK, and WAC. Conclusions We confirmed that the COQ4:c.370G>A, p.(Gly124Ser) variant, was a founder mutation among the Southern Chinese population. Screening for this mutation should therefore be considered while diagnosing Chinese patients suspected to have MDs. Furthermore, WES has proven to be useful in detecting variants in patients suspected to have MDs because it helps to obtain an unbiased and precise genetic diagnosis for these diseases, which are genetically heterogeneous.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.humgenomics.com-
dc.relation.ispartofHuman Genomics-
dc.rightsHuman Genomics. Copyright © BioMed Central Ltd.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectMitochondrial disease-
dc.subjectPaediatrics-
dc.subjectWhole-exome sequencing-
dc.titleDelineation of molecular findings by whole-exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population-
dc.typeArticle-
dc.identifier.emailKwong, AKY: kkyanna@hku.hk-
dc.identifier.emailFung, JLF: jasflf@connect.hku.hk-
dc.identifier.emailMak, CCY: ccymak@connect.hku.hk-
dc.identifier.emailYeung, KS: ksyyeung@hku.hk-
dc.identifier.emailChung, BHY: bhychung@hku.hk-
dc.identifier.emailFung, CW: fcw1209m@hku.hk-
dc.identifier.authorityChung, BHY=rp00473-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s40246-020-00278-0-
dc.identifier.pmid32907636-
dc.identifier.pmcidPMC7488033-
dc.identifier.scopuseid_2-s2.0-85090821291-
dc.identifier.hkuros314484-
dc.identifier.volume14-
dc.identifier.spagearticle no. 28-
dc.identifier.epagearticle no. 28-
dc.publisher.placeUnited Kingdom-

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