Clinical Characteristics,Genotypes And Pedigrees Of Pseudohypertrophic Muscular Dystrophy

Background:Muscular dystrophy pseudohypertrophy is a group of severe and progressive hereditary myopathy.Divided into DMD(Duchenne muscular dystrophy)and BMD(Becker muscular dystrophy)two types.Since DMD/BMD is an X-linked recessive hereditary disease,most of them are male,and DMD is the most common.There will be one patient in every 3500-5000 newborns in the world,and most female carriers have normal phenotypes.A small number of symptoms may appear,and it is a common disease among rare diseases.my country is one of the countries with the largest number of patients with the disease in the world.DMD is a serious disease and has a poor prognosis.Among the children born to female carriers,males have a 50%chance of developing the disease,and 50% of females are carriers of the diseasecausing gene.Improvements in child care and disease management have slowed disease progression,but current treatments fail to halt the relentless loss of muscle tissue and function,leading to premature death.Objective:To analyze the clinical characteristics of children with pseudohypertrophic muscular dystrophy,and to study the genotype of the children and the families of the probands to provide objective basis for clinical diagnosis,treatment and genetic counseling.Methods:A retrospective analysis of 33 patients with suspected pseudohypertrophic muscular dystrophy who visited the First Affiliated Hospital of Henan University of Science and Technology from March 2019 to December 2021.To analyze the clinical phenotypes of children with muscular dystrophy pseudohypertrophy,and use MLPA and next-generation sequencing to analyze the genetic mutation characteristics of the patients,and use Sanger sequencing to verify the gene status of some families.Results:1.There were 33 clinically suspected cases with chronic insidious onset and dissemination.There were 28 males and 5 females,aged between 1 and 23 years;There were 30 patients with DMD gene variants,including 25 large exon region deletions and 5 point mutations(c.10222 del A,c.5697 dup A,c.676＿678del,c.9917＿9923del,c.2168+1G>T).Three children with negative DMD gene,one of whom had a compound heterozygous variant of the LAMA2 gene,was diagnosed with limb-girdle muscular dystrophy;two had a TTN gene mutation.2.The detected large deletions of the DMD gene involved a total of 20 distinct regions,of which 18 caused frameshifts in the DMD protein-coding frame,6 caused in-frame deletions,and 1 caused loss of whole protein expression.3.Sanger sequencing was performed on the families of 10 children with DMD gene mutation,and it was found that the mothers of 3 probands had the same gene mutation as the children,and the other 7 children had no obvious abnormality in the families.The new mutation rate was(70%,7/10).Conclusion:1.Genetic testing of children with clinically suspected DMD/BMD,the results show that it is not entirely DMD gene mutation.2.For children with progressive muscular dystrophy combined with creatine kinase and other enzymatic changes and myogenic damage,it is recommended that MLPA be the first choice to detect the exon copy number of DMD gene.For patients with negative MLPA test,next-generation sequencing should be used to further analyze their genetic etiology;clinical attention should be paid to the differential diagnosis of other diseases such as DMD/BMD and limb-girdle muscular dystrophy.3.The results of genetic testing can guide the clinic to more accurately assess the medical history of children,intervene early,delay disease progression,and provide the basis for genetic counseling.4.In this study,5 cases of point mutations were found,namely c.5697 dup A,p.L1900 fs,c.10222 del A,p.T3408 fs,c.676＿678del,p.226 de,c.2168+1G>T and c.9917＿9923del,p.Thr3306 Serfs *22,these 5 variants are all de novo variants,not included in HGMD and other disease databases,and can be classified as pathogenic variants according to the American ACMG guidelines.