Study on Duchenne muscular dystrophy gene mutation and prenatal diagnosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the characteristics of DNA mutations underlying Duchenne muscular dystrophy and provide prenatal diagnosis.</p><p><b>METHODS</b>Multiplex ligation-dependent probe amplification (MLPA) and denaturing high performance liquid chromatography (DHPLC) were applied for analyzing DMD gene mutations in 388 unrelated Chinese patients and 53 fetuses.</p><p><b>RESULTS</b>Respectively, 230 and 43 subjects were found to harbor a deletion (59.28%) or duplication (11.08%). Two deletion hotspots were identified, which have located at exons 45-54 and exons 3-19. Duplications were mainly detected at exons 2-43. Point mutations were identified in 29.64% of patients. Fifty three fetuses were prenatal diagnosed, among which 18 were identified as patients.</p><p><b>CONCLUSION</b>Frequencies of DMD gene deletions and duplications in China are similar to global data. Prenatal diagnosis can help to reduce births of DMD patients.</p>

Correlation between genotypes and phenotypes in pseudohypertrophic muscular dystrophy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the correlation between genotypes and phenotypes in Chinese patients with pseudohypertrophic muscular dystrophy.</p><p><b>METHODS</b>Patients with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) were diagnosed clinically. Multiplex ligation-dependent probe amplification (MLPA) were performed to detect potential DMD gene mutations. The results were analyzed statistically.</p><p><b>RESULTS</b>Among 280 patients, 238(85.0%) were diagnosed with DMD, 35(12.50%) were diagnosed with BMD and 7(2.5%) were diagnosed with intermediate muscular dystrophin (IMD). Among these, 252(92.31%) were in-frame mutations, and 21(7.69%) were out-of-frame mutations. Twelve patients with DMD have carried in-frame mutations, 9 with BMD have carried frame-shift mutations, and 7 IMD patients have carried frame-shift mutation.</p><p><b>CONCLUSION</b>Most of the genotypes and phenotypes of DMD have complied with the reading-frame hypothesis. Patients with BMD with frame-shift mutations may facilitate understanding of the pathogenesis of DMD, and provide a theoretical basis for clinical therapy.</p>

Genotypic and clinical features of spinal muscular atrophy type 3 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genotypic and clinical features and laboratory examinations of spinal muscular atrophy type 3 (SMA III).</p><p><b>METHODS</b>Results of genetic testing and laboratory exams of 18 SMA III patients were collected and analyzed.</p><p><b>RESULTS</b>The average age of onset of patients was 6.1 years, with the course of disease lasting from 13 months to 28 years. All patients became symptomatic with lower extremity muscle weakness. The symptoms gradually aggregated, with proximal lower limb muscle becoming atrophic and proximal upper limb muscle becoming weak. Genetic testing indicated that all subjects possessed homozygous deletions of SMN1 gene. Electromyography (EMG) of 15 subjects indicated neurogenic damage. Whilst younger patients had normal level of creatine kinase (CK), elder patients had higher level of CK, though no linear correlation was found.</p><p><b>CONCLUSION</b>Full understanding of Clinical, especially the growth features of SMA III, in combination with genetic testing, can facilitate diagnosis and early intervention of the disease.</p>

Study of dystrophin gene non-deletion/duplication mutations causing Becker muscular dystrophy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutations in patients featuring Becker muscular dystrophy (BMD) and to enhance the understanding of non-deletion/duplication mutations of the dystrophin gene causing BMD.</p><p><b>METHODS</b>Clinical data of two patients affected with BMD were collected. Potential mutations in the dystrophin gene were screened with multiplex ligation-dependent probe amplification assay (MLPA). Biopsied muscle samples were examined with HE staining, immnostaining with anti-dystrophin antibody, and electronic microscopy.</p><p><b>RESULTS</b>MLPA assay suggested that both cases were probably due to non-deletion/duplication mutations of the dystrophin gene. Light and electronic microcopy of skeletal muscle biopsies confirmed dystrophic changes in both patients. For patient A, immunostaining showed non-contiguous weak staining for most parts of sarcolemma. For patient B, immunostaining showed positive result with N-terminal anti-dystrophin antibody and negative result with C-terminal anti-dystrophin antibody.</p><p><b>CONCLUSION</b>For patients with mild phenotypes but without dystrophin gene deletion/duplication, muscle biopsy and immunochemistry are helpful for diagnosis and prognosis.</p>

Study on clinical manifestation, genotype and genetic characteristics of two Kennedy disease pedigrees / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the clinical manifestations, genotypes, and genetic characteristics of two pedigrees with Kennedy disease.</p><p><b>METHODS</b>The clinical data of the patients from two Kennedy disease families were collected. The numbers of trinucleotide CAG repeats in exon 1 of the androgen receptor gene were determined by DNA sequencing and repeat fragment analysis.</p><p><b>RESULTS</b>Family A was composed of 58 individuals in 4 generations. The proband had onset at 39 years old. There were two Kennedy disease patients in family B which included 61 individuals in 5 generations. The two patients had onset at 39 and 41 years old, respectively. All the three patients displayed limbs and bulbar muscular weakness because of the damage of lower motor neurons. They had androgen insensitivity syndrome in common, and showed mild or moderate increase in serum creatine kinase level. The electromyogram showed wild damage in anterior horn of spinal cord. Muscle biopsy displayed neurogenic muscular atrophy. The numbers of the CAG repeat expansion in the androgen receptor gene of the three patients were 49, 48, and 47, respectively. X-linked recessive mode of inheritance was demonstrated by pedigree analysis in the two families.</p><p><b>CONCLUSION</b>Kennedy disease usually occurs in mid-adulthood man. The clinical features are the weakness and wasting of limbs and bulbar muscles. Genetic analysis contributes to diagnosis and identification of carriers, and is beneficial to genetic counseling and prenatal diagnosis.</p>