1/60. Maternally inherited cardiomyopathy: clinical and molecular characterization of a large kindred harboring the A4300G point mutation in mitochondrial deoxyribonucleic acid.OBJECTIVES: The purpose of this study was to describe the clinical and molecular features of a large family with maternally inherited cardiomyopathy (MICM). BACKGROUND: Recently, several mitochondrial deoxyribonucleic acid (mtDNA) point mutations have been associated with MICM. However, the distinctive clinical and morphologic features of MICM are not fully appreciated. This is partially due to the small size of the reported pedigrees, often lacking detailed clinical and laboratory information. methods: Clinical and genetic analysis of the family was carried out. RESULTS: echocardiography showed mostly symmetrical hypertrophic cardiomyopathy in 10 family members. The illness had an unfavorable course. Progressive heart failure occurred in three subjects, who eventually died; one individual underwent heart transplantation. Electrocardiographic or echocardiographic signs of cardiac hypertrophy in the absence of significant clinical complaints were observed in five subjects. neurologic examination was normal. The mutation was detected in blood from all available subjects. Abundance of mutated molecules ranged between 13% and 100% of total mtDNA genomes. The severity of the disease could not be foreseen by the proportion of mutation in blood. CONCLUSIONS: This report contributes a better description of the clinical aspects of MICM and provides important clues to distinguish it from hypertrophic cardiomyopathy. We suggest that mtDNA mutations, particularly in the transfer ribonucleic acid for isoleucin, should be systematically searched in patients with MICM. The identification of an underlying maternally inherited mitochondrial dna defect in familial cases of cardiomyopathy may considerably influence the management and genetic counseling of affected patients.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
2/60. Early onset of X-linked Emery-Dreifuss muscular dystrophy in a boy with emerin gene deletion.A boy developed contractures of the Achilles tendons at 3 years and of the postcervical muscles at 7 years, although neither contractures of the elbows nor cardiac abnormality were recognized by the age of 9 years. Muscle computed tomography scanning revealed changes characteristic of muscle involvement. Emerin was not detected in the biopsied muscle, and RT-PCR and PCR-based genomic dna analyses of the emerin gene demonstrated no amplification product in the patient. These results confirmed the diagnosis of X-linked Emery-Dreifuss muscular dystrophy (EDMD), and reinforce the necessity of molecular genetic diagnosis of the membrane protein emerin in younger patients with possible EDMD before appearance of the typical symptoms, to avoid sudden cardiac death.- - - - - - - - - - ranking = 211.08825134551keywords = muscular dystrophy, dystrophy (Clic here for more details about this article) |
3/60. Characterisation of two mutations in the ABCD1 gene leading to low levels of normal ALDP.A variety of mutations have been identified in the X-linked adrenoleukodystrophy (X-ALD) gene, none of which is prevalent. In this work we describe a reverse transcription polymerase chain reaction (RT-PCR)-based strategy specially suited to the molecular characterisation of mutations in index cases. After RT-PCR amplification of the X-ALD transcript a conformation-sensitive gel electrophoresis analysis is performed followed by sequencing of the fragments with altered mobility. Two X-ALD patients were studied using this strategy. In both cases, splice site mutations were found. The first patient studied has a single base substitution at the first position of the invariant GT dinucleotide donor splice site of intron 8. In spite of this alteration, small quantities of correctly spliced mRNA molecules were easily detected. In agreement with these data, a small amount of ALDP was found by western blotting analysis. An alteration at the -1 position of the donor splice site of exon 1 was detected in the second patient. This mutation results in the utilisation of a cryptic 5' splice site within intron 1. Nevertheless, this transition also allows for some correct splicing. Western blotting analysis revealed the existence of normal-migrating ALDP. However, as expected, the levels of this protein were greatly decreased. Taken together, our data suggest that some less severe or late-onset forms of X-ALD associated with splice mutations result from the production of small amounts of normal ALDP. It is proposed that the quantification of ALDP levels in these patients could provide important insights concerning the correlation between clinical phenotype and amount of normal ALDP.- - - - - - - - - - ranking = 1.4619287259192keywords = dystrophy (Clic here for more details about this article) |
4/60. Management of incontinentia pigmenti: a case of monolateral preretinal fibrovascular proliferations adjacent to snail-track degeneration areas.PURPOSE: To report a case of monolateral preretinal fibrovascularproliferations in a young adult woman, who had suffered from incontinentia pigmenti (IP) during her first month of life. methods: Case report. RESULTS: Circumscribed preretinal fibrovascular proliferations, adjacent to a mid-peripheral area of snail track degeneration, were occasionally diagnosed in the left eye of an asymptomatic 18-year-old white female. Careful ocular examination did not reveal any cause of the monolateral vascular abnormalities observed in the posterior segment. A detailed medical history brought to light that the patient has suffered infantile IP, like four other females in her family. The patient did not present any evident malformation of teeth, nails, skeleton or hair. A cytogenetic linkage study documented a chromosomal aberration in the Xq28 band, which confirmed the diagnosis of familial IP (type 2). The fluorescein angiography findings clearly illustrated the minimal retinal involvement in the course of IP. CONCLUSIONS: This case shows that a wide range of etiologies must be considered in patients presenting monolateral preretinal fibrovascular proliferations. To correctly manage these uncommon, inherited or acquired, retinal diseases it is better to do a mid-term follow-up, rather than operate immediately, and this enabled us to observe the natural course of the lesion, while awaiting a definitive diagnosis.- - - - - - - - - - ranking = 0.095246003722147keywords = ocular (Clic here for more details about this article) |
5/60. Early and severe presentation of X-linked myotubular myopathy in a girl with skewed X-inactivation.X-linked myotubular myopathy is a severe congenital myopathy in males, caused by mutations in the myotubularin (MTM1) gene on chromosome Xq28. In heterozygous carriers of MTM1 mutations, clinical symptoms are usually absent or only mild.We report a 6-year-old girl presenting at birth with marked hypotonia and associated feeding and respiratory difficulties. A muscle biopsy performed at 5 months suggested a diagnosis of myotubular myopathy. On examination at 6 years she had marked facial weakness with bilateral ptosis and external ophthalmoplegia, severe axial and proximal weakness and a mild scoliosis. Muscle magnetic resonance imaging showed a distinctive pattern of muscle involvement.Molecular genetic investigation of the MTM1 gene identified a heterozygous mutation in exon 12. X-inactivation studies in lymphocytes showed an extremely skewed pattern (97:3).This case emphasizes that investigation of the MTM1 gene and X-inactivation studies are indicated in isolated females with histopathological and clinical findings suggestive of myotubular myopathy.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
6/60. Mental retardation and early onset of weakness in a girl with a dystrophinopathy and a large Xp21-23 deletion.A 2-year-old girl presented with severe global developmental delay weakness, and an elevated serum creatine kinase level. Her muscle biopsy was consistent with an active dystrophy with absence of dystrophin in about half of the muscle fibers. Fluorescent in situ hybridization analysis showed her karyotype to be 46, X, delX p23.1-p21.1. This large deletion includes the dystrophin gene as well as the region involved in X-linked mental retardation. The genetic mechanism for the manifestation of both diseases is likely non-random inactivation of the x chromosome. To our knowledge, the combination of this dystrophinopathy in association with severe mental retardation has not been described in a girl.- - - - - - - - - - ranking = 1.4619287259192keywords = dystrophy (Clic here for more details about this article) |
7/60. Microphthalmia with linear skin defects syndrome (MLS): a male with a mosaic paracentric inversion of Xp.The microphthalmia with linear skin defects syndrome (MLS) is an X-linked dominant disorder with male lethality. In the majority of the patients reported, the MLS syndrome is caused by segmental monosomy of the Xp22.3 region. To date, five male patients with MLS and 46,XX karyotype ("XX males") have been described. Here we report on the first male case with MLS and an XY complement. The patient showed agenesis of the corpus callosum, histiocytoid cardiomyopathy, and lactic acidosis but no microphthalmia, and carried a mosaic subtle inversion of the short arm of the x chromosome in 15% of his peripheral blood lymphocytes, 46,Y,inv(X)(p22.13 approximately 22.2p22.32 approximately 22.33)[49]/46,XY[271]. By fluorescence in situ hybridization (FISH), we showed that YAC 225H10 spans the breakpoint in Xp22.3. End-sequencing and database analysis revealed a YAC insert of at least 416 kb containing the genes HCCS and AMELX, and exons 2-16 of ARHGAP6. Molecular cytogenetic data suggest that the Xp22.3 inversion breakpoint is located in intron 1 of ARHGAP6, the gene encoding the Rho GTPase activating protein 6. Future molecular studies in karyotypically normal female MLS patients to detect submicroscopic rearrangements including the ARHGAP6 gene as well as mutation screening of ARHGAP6 in patients with no obvious chromosomal rearrangements will clarify the role of this gene in MLS syndrome.- - - - - - - - - - ranking = 0.125keywords = myopathy (Clic here for more details about this article) |
8/60. Becker-type muscular dystrophy. Report of a family with one postmortem study.Becker-type muscular dystrophy (BMD) is reported in two brothers. In one of the patients, the molecular demonstration of an in-frame deletion of exons 45, 46 and 47 has confirmed the clinical and pathological diagnosis of BMD. The autopsy of the other patient revealed mild neuronal losses in the anterior horns at C8, lumbar and sacral levels of the spinal cord. Mild neuronal losses in the spinal cord may explain the mixed type of neurogenic-myogenic features in the skeletal muscles of adult BMD patients.- - - - - - - - - - ranking = 211.08825134551keywords = muscular dystrophy, dystrophy (Clic here for more details about this article) |
9/60. Phenotypic Duchenne muscular dystrophy with C-terminal domain.We report a patient with X-linked muscular dystrophy who had rapidly progressive muscle weakness and became wheelchair-bound at age 10 years. Clinically, he was diagnosed as having Duchenne muscular dystrophy; however, he was diagnosed as having Becker muscular dystrophy by dystrophin tests using a C-terminal monoclonal antibody. No immunolabelling was observed with a monoclonal antibody against the N-terminal domain. multiplex polymerase chain reaction analysis revealed the deletion of exons 3-19. The data suggest that the deletion of the N-terminal domain of dystrophin can cause a severe phenotype even when the C-terminus of the protein is well preserved.- - - - - - - - - - ranking = 295.52355188371keywords = muscular dystrophy, dystrophy (Clic here for more details about this article) |
10/60. myotonic dystrophy associated with 47 XYY syndrome.A case of myotonic dystrophy with 47 XYY presented with tall stature and mental retardation. The patient was a 37-year-old male. In addition to grip myotonia and percussion myotonia, severe weakness and atrophy were noted in the face and the neck muscles and in the distal muscles of the four limbs. He also had diabetes mellitus, cataracts and sexual behavior abnormalities. He was found to be 47 XYY from chromosomal examinations. The combination of 47 XYY syndrome and myotonic dystrophy has not been reported previously.- - - - - - - - - - ranking = 8.7715723555153keywords = dystrophy (Clic here for more details about this article) |
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