Novel PANK2 mutation discovered among South East Asian children living in Thailand affected with pantothenate kinase associated neurodegeneration.

Autor: Sakpichaisakul K; Division of Neurology, Department of Pediatrics, Queen Sirikit National Institute of Child Health, Ministry of Public Health, College of Medicine, Rangsit University, Bangkok, Thailand., Saengow VE; Department of Pediatrics, Maharat Nakhon Ratchasima Hospital, Nakhon Ratchasima, Thailand., Suwanpratheep P; Department of Pediatrics, Ratchaburi Hospital, Ratchaburi, Thailand., Rongnoparat K; Department of Pediatrics, Udon Thani Hospital, Udon Thani, Thailand., Panthan B; Center for Medical Genomics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Trachoo O; Center for Medical Genomics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Electronic address: objoon.tra@mahidol.ac.th.
Jazyk: angličtina
Zdroj: Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia [J Clin Neurosci] 2019 Aug; Vol. 66, pp. 187-190. Date of Electronic Publication: 2019 May 11.
DOI: 10.1016/j.jocn.2019.04.017
Abstrakt: Pantothenate kinase-associated neurodegeneration (PKAN) is linked to brain iron accumulation caused by PANK2 gene mutation. Despite the importance of genetic testing to confirm PKAN and identify at risk parents, genetic screening is financially burdensome for developing countries like Thailand. Because genetic screeners are expensive and not reimbursed by the universal health care coverage system, they are not typically performed. To investigate clinical symptoms, radiological findings and mutation analysis for patients based in Thailand with unknown genetic status but suspected PKAN based on clinical symptoms. Genetic testing was performed for cases suspected for PKAN and their biological parents by direct genomic sequencing of PANK2 at Maharat Nakhon Ratchasima Hospital during 2017-2018. Clinical evaluation and documentation were performed by pediatric neurologists. Five children had classical onset form of PKAN. Most presented with gait dystonia. Three patients diagnosed after 4 years showed the eye-of-the-tiger sign in their brain MRI, whereas two younger patients revealed only isolated hyperintensity bilateral globus pallidus. However, PANK2 mutations were identified in all cases: the most common mutation was c.982-1G>C. This mutation was detected in four unrelated individuals but not reported in other studies. Genetic testing is recommended to confirm diagnoses in cases with supporting clinical features of PKAN with or without the classical 'eye-of-the-tiger-sign'. A novel PANK2 mutation (c.982-1G>C) was identified in South East Asian populations based in Thailand, suggesting that this genetic variant is a founder genotype in this population. Moreover, genetic diagnosis is helpful to provide appropriate genetic counseling to families.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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