The Relationship Of Cognitive Function With Dp140 Expression In Patients With Duchenne's Muscular Dystrophy

ObjectiveDuchenne muscular dystrophy(DMD)is an X-linked recessive inherited disease.There is currently no cure for DMD.At present,related research mostly focus on motor function,cardiac system,respiration system,digestive system,and so on.The pathophysiological mechanism responsible for fatal muscle pathology in DMD are relatively well understood,and the disease is classically considerly neuromuscular in nature.Given this,it is perhaps not surprising that,even though the original description of the disorder noted decreased intellectual abilities,little attention has been paid to cognition or other neurobehavioral characteristics.There is,however,compelling evidence supporting central nervous system damage in DMD patients,for example,cognitive impairment,attention deficit hyperactivity disorder,autism spectrum disorder,obsessive-compulsive disorder,anxiety,depression and other mental behavior disorders.Cognitive impairment(IQ<70),a characteristic has been reported to been a very common clinical symptom of DMD.The incidence of cognitive impairment(IQ<70)has been reach up to 19% to 35%,which is much higher than that in normal children.DMD patients with cognitive impairment shows poor social adaptation and participation,which is related with low quality of life,impaired social function and limited access to education.Cognition impairment of DMD patients increased the burden of guardians.Some studies showed that mutations in the distal end of DMD gene have a more pronounced effect on patient's intelligence,possibly due to mutations affecting the expression of Dp140.Till now,there is no study on the correlation between Dp140 and cognitive impairment in Chinese DMD patients.This study is going to evaluate the cognitive characteristics and the relationship between cognition function and Dp140 expression in Chinese DMD patients.It may be useful for early detection of children with intellectual impairment and early clinical intervention to improve the quality of life of patients and guardians.MethodsFrom October 2014 to December 2017,122 patients with Duchenne muscular dystrophy were diagnosed by genetic testing or muscle biopsy at the Third Medical Center,Chinese People's Liberation Army General Hospital.According to patient's genotype,patients were divided into Dp140(+)group and Dp140(-)group.The Wechschild Intelligence Scale,version IV were used to assess patients' cognitive fuction by a trained doctor in a quiet room.The Wechschild Intelligence Scale Test include full scale intelligence quotient(FSIQ),verbal intelligence quotient(VIQ),and perform intelligence quotient(PIQ).Patients information,include patients' age,mutation characteristics,family history and medication situation.We compared the intelligence differences between the two groups.Results1.All 122 patients were male,with an age range of 6.0 to 13.3 years,and an average age of(8.1 ± 1.5)years.6 of the 122 patients could not walk and the rest preserve ambulation ability;Among the 122 patients,104 patients were treated with glucocorticoid,and the rest had not taken glucocorticoid.100 patients were with big mutation including 89 cases with deletion mutation and 11 cases with duplication mutation;22 patients were with small mutation including 10 cases with small deletion mutation,9 cases were with nonsense mutation,and only 1 case with splicing mutation,missense mutation and small insertion mutation.2.The intellectual scores of this group of DMD children were(93.34±16.31)in FSIQ,(91.52±15.97)in VIQ and(96.70±17.37)in PIQ.The scores was significantly lower than normal children(100 points,P <0.01),but significantly higher than the results of Cotton's Meta analysis in 2005 which include 1146 DMD patients [FSIQ(80.2 ± 19.3)points,VIQ(80.4 ±18.8)points,PIQ(85.4±16.9)points,P<0.01].FSIQ,VIQ,and PIQ scores in Dp140(+)group were(96.71±16.52),(95.09±14.97),(98.96±18.13),and(85.30±15.20),(83.65±16.30),(89.22±15.48)in Dp140(–)group.The difference between the two groups was statistically significant(P<0.01).ConclusionsThe intellectual level of this group of Chinese DMD children was lower than normal children.The proportion of mental impairment was significantly lower than that of foreign countries.Verbal intelligence quotient(VIQ)is more serious damaged than perform intelligence quotient(PIQ).DMD patients expressing Dp140 have higher WISC-? scores than than those without Dp140 expression.It suggest that intellectual impairment in DMD patients is associated with loss of Dystrophin protein expression in the central nervous system.