Gerhard Meng

Facioscapulohumeral muscular dystrophy presenting with isolated axial myopathy and bent spine syndrome

Several subtypes of facioscapulohumeral muscular dystrophy (FSHD) with atypical clinical presentation have been described. We report a new, distinct phenotype with progressive bent spine syndrome solely affecting the paraspinal muscles. Magnetic resonance imaging study of the lumbar spine revealed marked atrophy of the paraspinal muscles. The diagnosis was confirmed by DNA testing, which revealed shortened restriction fragments of the D4Z4 repeat on haplotype A in connection with a positive family history. Muscle Nerve 42:273–275, 2010

The dystrophin gene is autosomally located on a microchromosome in chicken.

The dystrophin gene has been mapped to a pair of microchromosomes in Gallus domesticus. In situ hybridization using a pool of biotinylated human cDNA probes allowed detection of this huge single-copy sequence without having to employ isotopic labeling. The autosomal nature of the DMD gene in chicken is supported by molecular data from quantitative Southern blot analysis and is in sharp contrast to that in all eutherian mammals studied, where it is a characteristically X-linked locus. With previous data taken into consideration, these results should prove significant in understanding the evolution of sex chromosomes during speciation as well as highlighting the importance of avian microchromosomes.

A genetic linkage map of five marker loci in and around the Duchenne muscular dystrophy locus

Linkage analysis of five marker loci in and around the Duchenne muscular dystrophy (DMD) locus, DXS84, DXS206, DXS164, DXS270, and DXS28, was conducted with 499 families. Overall, the best multipoint distances were found to be DXS84-3.7 +/- 0.6 cM-DXS206-1.0 +/- 0.4 cM-DXS164-1.9 +/- 0.6 cM-DXS270-12.0 +/- 1.1 cM-DXS28. A comparison of this linkage map with the established physical map suggests the presence of hot spots for recombination in the DMD locus.

Cardiac Involvement in Facioscapulohumeral Muscular Dystrophy

Cardiac involvement (CI) in form of myocardial thickening in a patient with genetically confirmed facioscapulohumeral muscular dystrophy (FSHMD) has not been reported. The patient is a 50-year-old male with a tandem repeat size of 17 and 14 kb in the D4Z4 locus on chromosome 4q35. The clinical cardiologic investigation was normal. Blood pressure was 150/90 mm Hg. Funduscopy, 24-hour ambulatory ECG, and 24-hour blood pressure monitoring were normal. ECG showed incomplete right bundle branch block, ST elevation in V2–V4, tall T waves in V3–V5, and hypertrophy signs. Echocardiography revealed left ventricular myocardial thickening of the posterior wall (11.7 mm) and the septum (15.5 mm). In conclusion, CI in genetically confirmed FSHMD may manifest not only as ECG abnormalities but also as left ventricular myocardial thickening.

The Genetic Approach: Next-Generation Sequencing-Based Diagnosis of Congenital and Infantile Myopathies/Muscle Dystrophies

The practical basis for massive parallel sequencing is described to help clinicians in choosing the most adequate diagnostic approach for childhood myopathies. The key quality feature for massive parallel sequencing is the sequence depth (coverage) as a prerequisite for variant identification and quantification of sequence copy numbers. Our experience with a next-generation sequencing gene panel for the analysis of muscular dystrophies/myopathies with infantile or juvenile onset resulted in the identification of pathogenic or likely pathogenic mutations in approximately 41% (of 141 patients), thus leading to a definitive diagnosis. A subset of patients shows an accumulation of “excess” heterozygous variants that may act as modifiers of the phenotype. Massive parallel sequencing has become a reliable and cost-effective method, but it requires exact clinical, bioptic, and/or radiologic information to evaluate the clinical relevance of possibly pathologic variants.

Progressive Respiratory Insufficiency in the Absence of Cardiac Disease in Late-Stage Duchenne Muscular Dystrophy

Not only the skeletal muscle but also the heart is frequently affected by the dystrophic process in Duchenne muscular dystrophy (DMD) patients[1][1] and DMD carriers.[2][2] Contrary to this paradigm, there are some reports showing absence of cardiac involvement in DMD, even in the late stages of the

Mapping Undetected Mutations within a Gene – Evidence for Two Preferential Regions in the DMD Gene

A maximum-likelihood method is developed to estimate the frequency distribution of undetected mutations (presumably point mutations, small deletions, insertions) along a gene, where the gene extends over a long stretch of DNA. In each family, the point of the mutation is potentially at a different location within the gene. In this sense, there is genetic heterogeneity among families and the method estimates the proportion of families whose mutation is at (or in the vicinity of) a given point inside the gene. Our method is applied to a sample of 75 families with Duchenne muscular dystrophy in which the disease mutation remained undetected. We find two preferential regions for these undetected mutations, with an estimated 85% of families having their mutation in one region and the remaining 15% of families in the other. The new method is expected to be useful in finding small mutations in any of the currently known large genes.