Delineation of molecular findings by whole-exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population
| Autor: | Brian H.Y. Chung, Che-Kwan Ma, Kate L.S. Chan, Shuk-Mui Tai, Anna K.Y. Kwong, Mandy H.Y. Tsang, Rachel Chan, Cheuk-Wing Fung, Jan A.M. Smeitink, Christopher C.Y. Mak, W.K. Chak, Shelia S.N Wong, Sharon T. H. Fung, Thomas Tsoi, Jasmine L.F. Fung, Richard J. Rodenburg, Shun-Ping Wu, Joannie Hui, Kit San Yeung, Victor Chi Man Chan, Mullin H.C. Yu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Oncology Mutation rate Mitochondrial Diseases lcsh:Medicine GTP Phosphohydrolases Mixed Function Oxygenases Cohort Studies 0302 clinical medicine Drug Discovery Child Exome sequencing education.field_of_study Nuclear Proteins Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] Homeobox Protein Nkx-2.2 Whole-exome sequencing Molecular Medicine Medical genetics Female Sodium-Potassium-Exchanging ATPase Primary Research China medicine.medical_specialty Mitochondrial DNA lcsh:QH426-470 Mitochondrial disease Population Mitochondrial Proteins 03 medical and health sciences Asian People Internal medicine Exome Sequencing Genetics medicine Humans Genetic Predisposition to Disease education Molecular Biology Homeodomain Proteins business.industry Genetic heterogeneity lcsh:R Paediatrics medicine.disease Human genetics lcsh:Genetics 030104 developmental biology Mutation business 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Human Genomics, 14, 1 Human Genomics, 14 Human Genomics Human Genomics, Vol 14, Iss 1, Pp 1-10 (2020) |
| ISSN: | 1479-7364 1473-9542 |
| Popis: | Background 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink