| BackgroundSpinocerebellar ataxias(SCAs)are autosomal dominant neurodegenerative disorders characterized by progressive cerebellar ataxia.SCAs mainly damage to the cerebellum and its efferent pathway.The clinical manifestations of SCAs are very complex,such as gait disturbance,difficulty with balance,intentional tremors,drinking water cough,dysarthria,deep sensory disorders,pyramidal tract sign and so on.SCAs are autosomal dominant disorders,so each child of an individual with SCA1 has a 50% chance of inheriting the expanded ATXN1 allele.There are multiple subtypes of spinocerebellar ataxia,and the genes and sites of mutations are not the same in each subtype.There is no significant difference in the age of onset of various types of SCAs.The clinical manifestations are similar and overlap with each other.It is difficult to distinguish the type of SCAs through clinical manifestations and imaging examinations.The annual increase in the scale for International cooperative ataxia rating scale(ICARS)and timing measurements of motor function have evaluated some common SCA types,showing that SCA1 appears to have a faster progression than other common types like SCA2,SCA3,SCA6,and SCA7.Epidemiological studies shown that approximately one to two individuals in 100,000 develop SCA1.Worldwide SCA1 represents approximately 6% of individuals with autosomal dominant cerebellar ataxia;this figure varies considerably based on geographic location and ethnic background.Spinocerebellar ataxia type 1(SCA1)is an aberrant repeat of the CAG sequence of the ATXN1 gene which located on autosome 6p22-23,which causes abnormal expanded polyglutamine chain when encoding the ataxia-1 protein and causes neurotoxicity.SCA1 is characterized by progressive cerebellar ataxia,dysarthria,and eventual deterioration of bulbar functions.At present,there are only the supportive therapies for the disease.on the contrary there is no specific treatment,which makes a great harm to patients and their families.Early genetic diagnosis makes important clinical and social value.Therefore,we inspected the SCA1 family in Henan Province.In the 8 members of the pedigree,including the four generations,we discuss the relationship among the age of onset,the clinical manifestations of molecular genetics,imaging findings,and neurophysiology in SCA1.ObjectiveIn this study,we investigate a SCA1 family that come from Fangcheng County,Henan Province.In order to get a better understand of the clinical,imaging,neurophysiological and molecular genetic features of spinocerebellar ataxia type 1(SCA1).Methods1.In this case,a SCAs family proband who came from Fangcheng County,Nanyang City,Henan Province,who was a patient at the Fifth Affiliated Hospital of Zhengzhou University.The proband was clinically diagnosed as Spinocerebellar ataxias considering clinical manifestations,family history,and imaging findings.The clinical diagnosis fits the Heading diagnostic criteria.In order to fully understand the clinical characteristics of the disease in the family,we conducted a survey of the family including family history,neurological examinations,and complete the pedigree diagrams.We also use of the International cooperative Ataxia Rating Scale(ICARS)to assess patients with positive clinical symptoms.2.After we inform patients of the significance of genetic diagnosis.We collect peripheral venous blood from 8 families of SCA1 family and place them in EDTA tube,including 4 generations,of which 4 are clinically symptomatic patients and 4 have no clinical symptoms.The serum samples were analyzed by PCR-STR analysis to determine the genotypes,CAG repeats of mutation sites were calculated,and diagnosis was made.Results1.The CAG sequence of ATXN1 gene was abnormally repeated in 8 individuals of the SCA family.There were 4 patients of the 4 generations who were female.The age of onset was among 36-46 years old.The proband III7 showed the symptom when she was 43 years old,and the symptoms were most serious.The III11 showed the sympton in her 36 years old who had the earliest onset age.The onset time of II6 was 46 years old but the clinical symptoms of her were the lightest.The symptom in the beginning of 4 patients was cerebellar ataxia,and the main manifestation was progressive walking instability.Accompanied by dysarthria,drinking water coughing,and development of up-gaze palsy.Magnetic resonance imaging showed cerebellar atrophy,besides II9 has thoracic spinal cord atrophy,neurophysiological examination showed various of abnormalities,and in 4 cases of patients the clinical symptoms were more serious.2.Genetic testing of 8 members of the family confirmed that the family was SCA1 type,and the number of CAG repeats of the 6 individuals II6,III7,III9,III11 were 39,44,44,45,respectively.The CAG repeats of IV16,IV18,IV19,and V24 with negative symptoms were 44.Conclusions 1.The SCA1 type is a uncommon type of spinocerebellar ataxia.The patients in thsSCA1 family all showed progressive cerebellar ataxia as the first place,accompanied by dysarthria,dysphia,and deterioration of bulbar functions.development of up-gaze palsy,etc.Magnetic resonance imaging showed cerebellar atrophy.The clinical manifestations of patients are fit with the typical performance of SCA1,but the clinical manifestations of different patients and the same patients in different stages are significantly different,the speed and severity of the progress in SCA1 is not the same,there is significant clinical and Genetic heterogeneity.2.For the SCA1 family of Henan Province diagnosed in this study,there is no obvious early-onset phenomenon among generations.3.The electrophysiological examination of the SCA1 family in this study shows special characteristics.The evoked potentials indicate different degrees of central and peripheral lesions,especially the abnormality in the BEAP examination is significantly different than in other examinations.The abnormality of the BEAP may become A characteristic clinical feature of SCA1.4.The clinical manifestations of each subtype of SCAs are complex and overlap among each other.There is no obvious specificity.Therefore,it is clear that the diagnosis and classification of SCAs cannot only rely on clinical manifestations and imaging features.It must be combined with genetic diagnosis.Furthermore the strategy of choosing molecular genetic testing can be guided by clinical features.Besides genetic counseling has important implications for families and societies... |
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