Exome sequencing in paediatric patients with movement disorders.

Autor: Kwong AK; Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China., Tsang MH; Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China., Fung JL; Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China., Mak CC; Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China., Chan KL; Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China., Rodenburg RJT; Radboud Centre for Mitochondrial Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands., Lek M; Department of Genetics, Yale School of Medicine, New Haven, USA., Huang S; Department of Genetics, Yale School of Medicine, New Haven, USA.; Affiliated Hospital of Nantong University, Nantong, China.; The First Affiliated Hospital, Nanjing Medical University, Nanjing, China., Pajusalu S; Department of Genetics, Yale School of Medicine, New Haven, USA.; Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.; Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia., Yau MM; Department of Paediatrics and Adolescent Medicine, Tseung Kwan O Hospital, Tseung Kwan O, Hong Kong SAR, China., Tsoi C; Department of Pediatrics, Centro Hospitalar Conde de Sao Januário Hospital, Macau SAR, China., Fung S; Department of Paediatrics and Adolescent Medicine, Kwong Wah Hospital, Yau Ma Tei, Hong Kong SAR, China., Liu KT; Department of Paediatrics and Adolescent Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong SAR, China., Ma CK; Department of Paediatrics and Adolescent Medicine, United Christian Hospital, Kwun Tong, Hong Kong SAR, China., Wong S; Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Ngau Tau Kok, Hong Kong SAR, China., Yau EK; Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Kwai Chung, Hong Kong SAR, China., Tai SM; Department of Paediatrics and Adolescent Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong SAR, China., Fung EL; Department of Paediatrics, Prince of Wales Hospital, Sha Tin, Hong Kong SAR, China., Wu NS; Department of Paediatrics, Queen Elizabeth Hospital, Yau Ma Tei, Hong Kong SAR, China., Tsung LY; Department of Paediatrics and Adolescent Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong SAR, China., Smeitink J; Radboud Centre for Mitochondrial Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands., Chung BH; Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China. bhychung@hku.hk.; Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Ngau Tau Kok, Hong Kong SAR, China. bhychung@hku.hk.; Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Pok Fu Lam, Hong Kong SAR, China. bhychung@hku.hk.; Department of Paediatrics and Adolescent Medicine, The Duchess of Kent Children's Hospital, Pok Fu Lam, Hong Kong SAR, China. bhychung@hku.hk.; Department of Pediatrics, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. bhychung@hku.hk., Fung CW; Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China. fcw1209m@hku.hk.; Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Ngau Tau Kok, Hong Kong SAR, China. fcw1209m@hku.hk.
Jazyk: angličtina
Zdroj: Orphanet journal of rare diseases [Orphanet J Rare Dis] 2021 Jan 15; Vol. 16 (1), pp. 32. Date of Electronic Publication: 2021 Jan 15.
DOI: 10.1186/s13023-021-01688-6
Abstrakt: Background: Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis.
Results: We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation.
Conclusions: A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management. The study highlights the potential of implementing precision medicine in the patients.
Databáze: MEDLINE
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