Analysis Of Clinical Characteristics And Mutation Analysis Of A Family With Frontotemporal Dementia Associated With MAPT Gene Mutation

BackgroundFrontotemporal lobar degeneration,less than Alzheimer disease,is the second most common early-onset dementia.The features of pathology and image of FTD are characterized by the selective degeneration of the frontal and temporal lobes.Mental and behavioral abnormalities,language disorders and progressive executive dysfunction are the mainly clinical manifestation of frontotemporal dementia.It is estimated that about 40%-50% of FTD patients have a positive family history and 10.2%-27% have an autosomal dominant presentation.In the last few years many genes have been shown to cause autosomal dominant forms of FTLD,such as microtubule-associated protein tau(MAPT)gene,fused in sarcoma(FUS)gene,trans-active response DNA-binding protein of 43 kDa(TARDBP)gene,charged multifunctional protein 2B(CHMP 2B),granulin(GRN)gene,progranulin(PGRN)gene,valosin-containing protein(VCP)gene and so on.The first discovered gene which is associated with FTD is the MAPT gene.It is also the most common and important gene.There are 44 kinds of mutations of MAPT have been found,infecting 134 families.The p.P301 L mutation is one of the most common mutations in the MAPT gene involved in 32 families.Few cases of MAPT mutation have been reported in China.In this study,we reported a Han family which has a mutation of MAPT in Henan,China,and analyzed the characteristics of gene mutation and clinical features of the family.ObjectiveTo analyze the characteristics of gene mutation,clinical features and image characteristics of a family with behavioral variant of frontotemporal lobar degeneration(bv-FTD).Methods1.Case collection: A family with bv-FTD was clinically diagnosed by the Department of Neurology,Henan Provincial People’s Hospital.Detailed clinical history,the physical examination,laboratory examination,imaging examination and neuropsychological assessment of the proband and her family members were collected.Then drawing the pedigree of the family.2.Gene detection: Using Sanger sequencing and polymerase chain reaction,peripheral blood samples of the proband and other family members were tested for the microtubule associated protein tau gene(MAPT),exons 16 and 17 of amyloid precursor protein gene(APP),presenilin 1(PSEN1)and presenilin 2(PSEN2).Result1.Clinical features of this family: This frontotemporal dementia family is from Han nationality,China,.6 patients were found in this 5 generations,only the proband is still alive,the another 5 patients were dead.The age of onset in this family was 47-63 years old.Families have the similar clinical manifestations of bv-FTD were found in this family,but no symptoms of Parkinson’s disease were observed.This family showed autosomal dominant inheritance.2.The mainly clinical features of the proband were cognitive decline such as repetitive speech,euphoria,abnormal mental behavior,and executive function defunction.But no symptoms of Parkinson’s disease and memory loss were observed.MRI showed asymmetrical frontotemporal atrophy,especially on the left side.The FDG-PET metabolic imaging characteristics showed decreased metabolism in the corresponding frontotemporal region and mild metabolic reduction in the basal ganglia.3.The results of genetic test: By sanger sequencing,the proband was found with the c.1907 C > T mutation in exon 10 of the MAPT gene,at position 301 resulting amino acid proline(P)instead of leucine(L).The same mutation was also observed in one of her sibling and her two children.No mutations were observed in exons 16 and 17 of amyloid precursor protein(APP),presenilin 1(PSEN1)and presenilin 2(PSEN2).ConclusionWe report a family with the MAPT P301 L mutation in Henan Han population presented as bv-FTD.Structural imaging showed asymmetric frontotemporal atrophy,and functional imaging showed hypoperfusion in the corresponding region.Neuroimaging and genetic tests are helpful in the diagnosis of dementia in patients with a positive family history.