Clinical And Genetic Characteristics Of Frontotemporal Dementia With Amyotrophic Lateral Sclerosis:One Case Report And Literature Review

Objective To report a case of frontotemporal dementia with amyotrophic lateral sclerosis(FTD-ALS),review the relevant literature reported and then summarize the clinical and genetic characteristics of FTD-ALS patients.Methods We reported a patient of FTD-ALS who went to neurology department in the First Affiliated Hospital,Anhui Medical University in May 2017.After diagnosis,detailed clinical data of this patient was collected.We used the Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(Mo CA)and other neuropsychiatric scales to evaluate the cognitive function of this patient.The anticoagulant blood collection tubes containing EDTA were used to collect 5ml of peripheral venous blood from the patient as well as his first-degree relatives,and then these samples were stored at-20?.DNA of these blood samples were extracted with extraction kits.1.5?g of each DNA sample was breaking up by ultrasonication to obtain a 50-200 bp DNA fragment,thereby constructing a DNA library.The DNA library samples were vacuum-concentrated for hybridization capture,and the captured DNA samples were taken for high-throughput sequencing.The sequencing data was evaluated by the Illumina Sequential Control System(SCS)in the United States for data reading and bioinformatics analysis.Chinese FTD-ALS patients reported in detail were reviewed and the clinical and genetic characteristics of the disease were summarized.Results The patient,a 49-year-old man,responded slowly with impaired confrontation naming and impaired single-word comprehension.Magnetic resonance imaging showed temporal lobe atrophy.Besides,the patient gradually developed atrophy in limbs and bulbar muscles as well as spasticity of arms and legs,with pathological and primitive reflexes positive.Electromyography suggested a wide range of neurogenic changes,which were consistent with the FTD-ALS diagnostic criteria.A new heterozygous mutation(c.1335G>A chr12:64879792 p.W445X)was found in the TBK1 gene.The reference to the American College of Medical Genetics and Genomics guidelines suggested that this mutation type is likely pathogenic,which has not been reported by the Human Gene Mutation Database.There were a total of 25 Chinese FTD-ALS patients(including this case)reported in detail,including 15 males and 10 females.The average age of onset was(58.44±8.40)years old.Most of them had typical manifestations of FTD as the first symptom,followed by ALS.The interval between two different kinds of symptoms was 11.86±7.01 months.9 patients had genetic data analyses,7 of which had positive results.The mutations were TBK1 gene(2 cases),C9orf72,TRPM7,DCTN1,TARDBP,and ?-globulin genes,respectively.Most cases were sporadic FTD-ALS(including this example),and only 3 cases were family FTD-ALS.Conclusions FTD-ALS is a relatively rare disease,mostly sporadic,with a younger onset age,in which behavioral variant FTD is the main manifestation of dementia in the context of ALS,and cognitive impairment is earlier than ALS.In addition to C9orf72 gene,TBK1 gene is also an important pathogenic gene of FTD-ALS.Genetic analysis is of great value in the early diagnosis of FTD-ALS.