Genetic Analysis And Clinical Study Of15Chinese Children With PANK2-associated Neurodegeneration

Objective to analysis genetic and clinical on15Chinese children withclinically diagnosed Pantothenate Kinase-AssociatedNeurodegeneration(PKAN).Methods We recruited Pantothenate Kinase-Associated Neurodegeneration(PKAN) patients according to criteria proposed by diagnostic criteria for HSS werefirst proposed by Dooling et al. DNA of patients and their family members wasextracted from peripheral blood after informed consent.We can conclude from theDNAStar(DNAStar, Inc., Madison, WI).Results All patients are classical PKAN.With the disease’s symptomsprogress gradually,5cases (33.3%) have cognitive decline,4cases(26.7%) havedecreased vision,1case(6.7%) has athetosis,10cases (66.7%) have losed the abilityto walk alone, and7cases (46.7%)have dysarthria.8cases in patients examined withneuro-ophthalmologic exams and there were4cases (50%) pigmentary retinaldegeneration.We report the mutations including21gene mutations, which has6(28.6%)reported mutations：PANK2e1c.115G>T p.E39X， PANK2e5c.1172T>C p.I391T，PANK2e5c.1172T>A p.I391N，PANK2e4c.989G>C p.R330P， PANK2e2c.526C>Tp.R176C， PANK2e2c.460C>T p.R154W and15(71.4%) unreported mutations：PANK2e4c.940C>T p.L314F，PANK2e1c.67A>G p.M23V，PANK2e1c.53G>Ap.R18Q，PANK2e2c.391G>A p.E131K，PANK2e5c.1139C>T p.A380V，PANK2e2c.640G>T p.D214Y，PANK2e6c.1300G>T p.G434V，PANK2e2c.611C>G p.T204S，PANK2e1c.274G>A p.E92K， PANK2e1c.145DelC p.R49fsX94，PANK2e4c.995A>G p.D332G，PANK2e2c.314G>A p.G105E，PANK2e6c.1242G>Cp.L414F，PANK2e3c.691T>G p.C231G，PANK2e4c.1025A>G p.D342G. In thesemutations one is nonsense mutation, one is small missing and the rest are missense mutations.It shows eye-of-the-tiger sign in brain MRI. Patients7，11，13，14，15did CTexamination,but only CT of patient15don′t have high signal.Others have highsingnal.Conclusion1. This research on pantothenate kinase-2associated neurodegeneration (PKAN)in Chinese children has clinical and gene mutations analysis. In this group15childrenare typical PKAN. This research prompted that children in China with PANK2genemutations may different from other ethnics.2．PANK2gene mutations we find have21species, in which71.3percent isunreported mutations. This research for children with family of genetic advisory andthe prenatal diagnosis has important significance. Diagnosising for pregnant womencan reduce the incidence of this disease. It should carry on the early recoveryintervention to the patients and improve patient’s survival quality by the time.3.80%patients have high signal in CT which was not reported in otherresearches. CT is earlier than MRI.