Abstract：Objective To study the phenotypes and genetic features of families with Duchenne muscular dystrophy (DMD). Methods Seven children from six families with DMD diagnosed by gene testing were enrolled. The clinical and genetic features of the families were analyzed. Results There were two new mutations and four maternal inheritance mutations in the six families. The proband of family 1 had one point de novo mutation and one insertion de novo mutation of the DMD gene. Three families had point mutation, one family had fragment deletion of exon, and one family had fragment duplication of exon. The youngest age of onset of the probands was 6 months. All probands had skeletal muscle dyskinesia and significant changes in muscle enzymes, with different severities of clinical phenotypes. Three probands had mild mental retardation. The results of echocardiography were normal for all probands. The mother of the proband in family 6 had mild clinical phenotype. Conclusions Gene testing can be used for the confirmed diagnosis of DMD. Mental retardation is a frequent clinical phenotype of DMD. The symptoms of myocardial involvement are not obvious in the early stage. Female carriers may have mild clinical symptoms.
YANG Li,XU Xiao-Yan,ZHU Jing et al. Clinical phenotypes and genetic features of families with Duchenne muscular dystrophy[J]. CJCP, 2020, 22(8): 867-873.
Mah JK, Korngut L, Fiest KM, et al. A systematic review and meta-analysis on the epidemiology of the muscular dystrophies[J]. Can J Neurol Sci, 2016, 43(1):163-177.
[2]
Carter JC, Sheehan DW, Prochoroff A, et al. Muscular dystrophies[J]. Clin Chest Med, 2018, 39(2):377-389.
[3]
Anand A, Tyagi R, Mohanty M, et al. Dystrophin induced cognitive impairment:mechanisms, models and therapeutic strategies[J]. Ann Neurosci, 2015, 22(2):108-118.
[4]
Ricotti V, Mandy WP, Scoto M, et al. Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations[J]. Dev Med Child Neurol, 2016, 58(1):77-84.
[5]
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants:a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5):405-424.
[6]
Mercuri E, Bönnemann CG, Muntoni F. Muscular dystrophies[J]. Lancet, 2019, 394(10213):2025-2038.
[7]
Echigoya Y, Lim KRQ, Nakamura A, et al. Multiple exon skipping in the Duchenne muscular dystrophy hot spots:prospects and challenges[J]. J Pers Med, 2018, 8(4):41.
[8]
Bladen CL, Salgado D, Monges S, et al. The TREAT-NMD DMD Global Database:analysis of more than 7,000 Duchenne muscular dystrophy mutations[J]. Hum Mutat, 2015, 36(4):395-402.
[9]
Juan-Mateu J, Gonzalez-Quereda L, Rodriguez MJ, et al. DMD mutations in 576 dystrophinopathy families:a step forward in genotype-phenotype correlations[J]. PLoS One, 2015, 10(8):e0135189.
[10]
Birnkrant DJ, Bushby K, Bann CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1:diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management[J]. Lancet Neurol, 2018, 17(3):251-267.
[11]
Aartsma-Rus A, Ginjaar IB, Bushby K. The importance of genetic diagnosis for Duchenne muscular dystrophy[J]. J Med Genet, 2016, 53(3):145-151.
[12]
Okubo M, Minami N, Goto K, et al. Genetic diagnosis of Duchenne/Becker muscular dystrophy using next-generation sequencing:validation analysis of DMD mutations[J]. J Hum Genet, 2016, 61(6):483-489.
[13]
Hoogland G, Hendriksen RGF, Slegers RJ, et al. The expression of the distal dystrophin isoforms Dp140 and Dp71 in the human epileptic hippocampus in relation to cognitive functioning[J]. Hippocampus, 2019, 29(2):102-110.
[14]
Vaillend C, Chaussenot R. Relationships linking emotional, motor, cognitive and GABAergic dysfunctions in dystrophin-deficient mdx mice[J]. Hum Mol Genet, 2017, 26(6):1041-1055.
[15]
Bianchi R, Eilers W, Pellati F, et al. Hippocampal synaptic and membrane function in the DBA/2J-mdx mouse model of Duchenne muscular dystrophy[J]. Mol Cell Neurosci, 2020, 104:103482.
[16]
Doorenweerd N, Straathof CS, Dumas EM, et al. Reduced cerebral gray matter and altered white matter in boys with Duchenne muscular dystrophy[J]. Ann Neurol, 2014, 76(3):403-411.
[17]
Mavrogeni SI, Markousis-Mavrogenis G, Papavasiliou A, et al. Cardiac involvement in Duchenne muscular dystrophy and related dystrophinopathies[J]. Methods Mol Biol, 2018, 1687:31-42.
[18]
Huijben J, Jansen M, Ginjaar IB, et al. What can we learn from assisted bicycle training in a girl with dystrophinopathy? A case study[J]. J Child Neurol, 2015, 30(5):659-663.
[19]
Power LC, O'Grady GL, Hornung TS, et al. Imaging the heart to detect cardiomyopathy in Duchenne muscular dystrophy:a review[J]. Neuromuscul Disord, 2018, 28(9):717-730.
[20]
Leiner T, Strijkers G. Advances in cardiovascular MR imaging[J]. MAGMA, 2018, 31(1):3-6.
[21]
Verhaart IEC, Aartsma-Rus A. Therapeutic developments for Duchenne muscular dystrophy[J]. Nat Rev Neurol, 2019, 15(7):373-386.
