Novel mutations in PANK2 and PLA2G6 genes in patients with neurodegenerative disorders: two case reports

BMC Medical Genetics

Case Report

Mohammad Ali Faghihi¹  Hassan Dastsooz²  Majid Fardaei³  Mohammad Ali Farazi Fard⁴  Hamid Nemati⁵ 

[1] Center for Therapeutic Innovation and Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, USA;Comprehensive Medical Genetic Center, Shiraz University of Medical Sciences, Shiraz, Iran;Comprehensive Medical Genetic Center, Shiraz University of Medical Sciences, Shiraz, Iran;Department of Medical Genetics, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran;Department of Medical Genetics, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran;Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;

关键词: PLA2G6;    PKAN;    NBIA;    PANK2;    Case report;   

DOI  :  10.1186/s12881-017-0439-y

 received in 2016-11-05, accepted in 2017-07-13,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundNeurodegeneration with brain iron accumulation (NBIA) is a genetically heterogeneous group of disorders associated with progressive impairment of movement, vision, and cognition. The disease is initially diagnosed on the basis of changes in brain magnetic resonance imaging which indicate an abnormal brain iron accumulation in the basal ganglia. However, the diagnosis of specific types should be based on both clinical findings and molecular genetic testing for genes associated with different types of NBIA, including PANK2, PLA2G6, C19orf12, FA2H, ATP13A2, WDR45, COASY, FTL, CP, and DCAF17. The purpose of this study was to investigate disease-causing mutations in two patients with distinct NBIA disorders.Case presentationWhole Exome sequencing using Next Generation Illumina Sequencing was used to enrich all exons of protein-coding genes as well as some other important genomic regions in these two affected patients. A deleterious homozygous four-nucleotide deletion causing frameshift deletion in PANK2 gene (c.1426_1429delATGA, p.M476 fs) was identified in an 8 years old girl with dystonia, bone fracture, muscle rigidity, abnormal movement, lack of coordination and chorea. In addition, our study revealed a novel missense mutation in PLA2G6 gene (c.3G > T:p.M1I) in one and half-year-old boy with muscle weakness and neurodevelopmental regression (speech, motor and cognition). The novel mutations were also confirmed by Sanger sequencing in the proband and their parents.ConclusionsCurrent study uncovered two rare novel mutations in PANK2 and PLA2G6 genes in patients with NBIA disorder and such studies may help to conduct genetic counseling and prenatal diagnosis more accurately for individuals at the high risk of these types of disorders.

【 授权许可】

CC BY   
© The Author(s). 2017