[Clinical features of patients with Becker muscular dystrophy and deletions of the rod domain of dystrophin gene].

OBJECTIVE To explore the clinical features of patients carrying deletions of the rod domain of the dystrophin gene. METHODS Clinical data of 12 Chinese patients with Becker muscular dystrophy (BMD) and such deletions was reviewed. RESULTS Most patients complained of muscle weakness of lower limbs. Two patients had muscle cramps, one had increased creatine kinase (CK) level, and one had dilated cardiomyopathy. CONCLUSION Compared with DMD, the clinical features of BMD are much more variable, particularly for those carrying deletions of the rod domain of the dystrophin gene. Muscular weakness may not be the sole complaint of BMD. The diagnosis of BMD cannot be excluded by moderately elevated CK. For male patients with dilated cardiomyopathy, the possibility of BMD should be considered.

[Analysis of SMN1 gene mutations in 78 patients with spinal muscular atrophy].

OBJECTIVE: To explore the significance of SMN1 gene mutations among patients with spinal muscular atrophy (SMA) and the value of multiplex ligation dependent probe amplification (MLPA) for its diagnosis. METHODS: Potential mutations of the SMN1 gene were detected among 78 SMA patients with a MLPA assay. RESULTS: Homozygous deletion of SMN1 exons 7 and 8 was detected in 70 (89.7%) of all patients. Homozygous deletion of exons 7 and heterozygous deletion of exon 8 was detected in 3 patients (3.8%). Homozygous deletion of SMN1 exons 7 alone was detected in 3 patients (3.8%). Heterozygous deletion of SMN1 exons 7 and 8 was detected in 2 patients (2.6%). For 77 of the patients, both parents were found to carry heterozygous deletion of the SMN1 gene, which was consistent with the recessive inheritance of SMA. One patient with SMA type I was found to be rather rare. The patient was found to carry homozygous deletion of SMN1 exons 7 and 8, for which her mother was heterozygous, while no mutation was found in her father. CONCLUSION: Homozygous deletion of the SMN1 gene have been detected in more than 95% of SMA patients. No homozygous deletion of exon 8 has been found. Homozygous deletion of exon 7 is more significant in the pathogenesis of SMA.

[Clinical, familial and hereditary analysis of myotonic dystrophy].

OBJECTIVE: To analyze the clinical, familial and hereditary features of myotonic dystrophy to improve the knowledge and provide molecule evidence for gene diagnosis and prenatal diagnosis of myotonic dystrophy or dystrophia myotonia (DM) families. METHODS: Clinical data of 2 DM families were collected based on the probands. The number of trinucleotide CTG repeat in the 3' untranslated region of myotonic dystrophy protein kinase (DMPK) gene on chromosome 19 was determined by DNA sequence and repeat fragment. RESULTS: Except for 1 subclinical patient, another 5 patients progressed slowly with the features of myotonic muscular weakness and atrophy. One patient had hatchet face, 1 had cataract and diabetes mellitus, and the other 3 were bald. Electromyologram showed 3 patients had myotonic discharge and myopathic abnormalities. The number of trinucleotide CTG repeat in the 3' untranslated region of DMPK gene of 5 patients exceeded 50. CONCLUSION: DM can be anticipated. Gene analysis can verify the disease and identify subclinical patients. It helps to prevent the DM births by hereditary consultation performing prenatal diagnosis.

Detection of α-globin gene deletion and duplication using quantitative multiplex PCR of short fluorescent fragments.

BACKGROUND: The aim of this study was to establish a sensitive method that can detect the presence of not only the common but also the unusual or unknown α-globin gene deletions for screening of α-thalassemia. We used quantitative multiplex PCR of short fluorescent fragments (QMPSF) for the α-globin genes (HBA) to screen α-thalassemia deletions. METHODS: We set up and validated HBA-QMPSF using 50 negative and 100 positive controls of deletional α-thalassemia. To evaluate its ability to detect the presence of the common and unusual or unknown α-globin gene deletions, 579 unrelated samples were simultaneously analyzed using this assay and multiplex Gap polymerase chain reaction (Gap-PCR). The inconsistent results were further confirmed by multiplex ligation-dependent probe amplification (MLPA). RESULTS: HBA-QMPSF was capable of detecting α-globin gene deletions with an acceptable variability as shown by mean values (SD) of allele dosage for the heterozygous deleted control obtained from intra- and inter-experimental replicates [0.63 (0.01) and 0.61 (0.03)]. In 572 out of the 579 unrelated subjects, HBA-QMPSF and multiplex Gap-PCR gave consistent results. In seven cases which were finally proved to be composed of one rare deletion--Thai/-α3.7, one novel deletion--SEA/-α2.8, four αααanti3.7/αα and one αααanti4.2/αα triplications, HBA-QMPSF showed deletion or duplication in the α-globin gene while multiplex Gap-PCR failed to give the correct diagnosis. CONCLUSIONS: HBA-QMPSF is able to detect the presence of the common and unusual or unknown α-thalassemia deletions and duplications. It can be used as an initial screening test for α-thalassemia caused by HBA gene copy number alteration.

[Study on clinical manifestation, genotype and genetic characteristics of two Kennedy disease pedigrees].

OBJECTIVE: To investigate the clinical manifestations, genotypes, and genetic characteristics of two pedigrees with Kennedy disease. METHODS: 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. RESULTS: 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. CONCLUSION: 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.