Molecular Analysis of Patients With Neuromuscular Disease

The purpose of this study is to identify genes and proteins responsible for specific muscle disorders by studying genetic material from individuals with neuromuscular disease, as well as their family members. We are interested in recruiting many types of neuromuscular disease including; Duchenne and Becker muscular dystrophy DMD/BMD, limb-girdle muscle dystrophy LGMD. There are still many patients diagnosed with muscular dystrophy but have no causative gene implicated in their disease. We feel that these patients may have new genetic changes in genes coding for important muscle proteins that we have yet to identify. Using molecular genetics to unravel the biochemical basis of these neuromuscular disorders should lead to more accurate diagnosis of these disorders and should lead to potential therapies.

Our research has many goals, one of which is to characterize the genetic changes responsible for the type of muscle disease found in our participants. In our past research, several new genes responsible for various forms of neuromuscular disease were identified and/or are being studied. These include dystrophin, the sarcoglycans, obscurin, and filamin. Each discovery has resulted in advances in our ability to develop diagnostic tests which benefit patients and their families by providing accurate diagnosis, presymptomatic and/or prenatal testing. Genotype-phenotype correlation studies have increased our understanding of the natural history of these rare disorders benefiting patients through better prognostic determinations by clinicians. Biochemical and pathological analysis of muscle biopsies has led to new insights into disease pathophysiology which we hope will aid in finding treatments.

Our research also studies gene expression in muscle biopsy samples. This entails identifying the genes whose expression is increased or decreased in the muscles of individuals with different muscular dystrophy types. We believe these studies will identify genes and gene pathways which are common to the pathogenesis of muscular dystrophy or which are unique to a particular dystrophy. Our microarray research should lead to a better understanding of the disease process and possible ways to halt the process. The end point of these studies would be an accurate description of the disease pathogenesis.

Families will be ascertained world-wide as the muscular dystrophies are a pan-ethinic group of diseases.

• Limb-girdle Muscular Dystrophy
• Duchenne Muscular Dystrophy
• Becker Muscular Dystrophy
• Facioscapulohumeral Muscular Dystrophy

• Kang PB, Kho AT, Sanoudou D, Haslett JN, Dow CP, Han M, Blasko JM, Lidov HG, Beggs AH, Kunkel LM. Variations in gene expression among different types of human skeletal muscle. Muscle Nerve. 2005 Oct;32(4):483-91.
• Liadaki K, Kho AT, Sanoudou D, Schienda J, Flint A, Beggs AH, Kohane IS, Kunkel LM. Side population cells isolated from different tissues share transcriptome signatures and express tissue-specific markers. Exp Cell Res. 2005 Feb 15;303(2):360-74. Epub 2004 Nov 11.
• Guyon JR, Mosley AN, Jun SJ, Montanaro F, Steffen LS, Zhou Y, Nigro V, Zon LI, Kunkel LM. Delta-sarcoglycan is required for early zebrafish muscle organization. Exp Cell Res. 2005 Mar 10;304(1):105-15. Epub 2004 Dec 8.

The samples used in this study will be derived from individuals at risk for, or suffering from, neuromuscular disease, generally resulting in clinical weakness of one or more muscle groups.

Inclusion criteria:

1. having a clinical and/or pathological diagnosis of a muscular dystrophy
2. being the first degree relative of someone with such a diagnosis
3. having had a muscle biopsy if diagnosed with a neuromuscular disease

Exclusion Criteria:

1. not having such a diagnosis and not being related to such an individual
2. not wishing to participate
3. being incapable of giving consent and not having a legal guardian willing or able to do so