Guja Astrea1, Iulia Munteanu2, Denise Cassandrini3, Suzanne Lillis2, Rosanna Trovato3, Elena Pegoraro4, Giovanni Cioni5, Eugenio Mercuri6, Francesco Muntoni2, Roberta Battini7. 1. Department of Developmental Neuroscience, IRCCS Stella Maris, Pisa, Italy. 2. The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK. 3. Molecular Medicine, IRCCS Stella Maris Scientific Institute, Pisa, Italy. 4. Neuromuscular Center, Department of Neuroscience, University of Padova, Padua, Italy. 5. Department of Developmental Neuroscience, IRCCS Stella Maris, Pisa, Italy; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. 6. Department of Paediatric Neurology, Catholic University, Rome, Italy. 7. Department of Developmental Neuroscience, IRCCS Stella Maris, Pisa, Italy. Electronic address: r.battini@fsm.unipi.it.
Abstract
BACKGROUND: Congenital myopathies are inherited primary disorders of the muscle caused by mutations affecting structural, contractile, or regulatory proteins. In the more than 20 genes associated to these conditions, ryanodine receptor type 1 gene (RYR1) is responsible for the most common forms and is associated with a wide range of clinical phenotypes and pathological findings. Magnetic resonance imaging of muscle has been used increasingly to direct genetic testing in myopathies. PATIENT DESCRIPTION: We describe a consanguineous family affected by cystinuria type B, a metabolic condition linked to chromosome 19q13.2, and a different muscle phenotype that, although related to a congenital myopathy, does not have the striking histological features helping in direct genetic tests. RESULTS: The assessment of the selective involvement on muscle magnetic resonance imaging allowed the suspicion of RYR1 as the most likely gene responsible for this myopathy. The diagnosis was subsequently confirmed by the finding of a recessive RYR1 mutation. CONCLUSIONS: The occurrence of congenital myopathy together with cystinuria type B is reported for the first time. The use of muscle magnetic resonance imaging and the homozygosity by descent in SLC7A9, a gene flanking RYR1, allowed us to discover a new mutation in the RYR1 gene.
BACKGROUND:Congenital myopathies are inherited primary disorders of the muscle caused by mutations affecting structural, contractile, or regulatory proteins. In the more than 20 genes associated to these conditions, ryanodine receptor type 1 gene (RYR1) is responsible for the most common forms and is associated with a wide range of clinical phenotypes and pathological findings. Magnetic resonance imaging of muscle has been used increasingly to direct genetic testing in myopathies. PATIENT DESCRIPTION: We describe a consanguineous family affected by cystinuria type B, a metabolic condition linked to chromosome 19q13.2, and a different muscle phenotype that, although related to a congenital myopathy, does not have the striking histological features helping in direct genetic tests. RESULTS: The assessment of the selective involvement on muscle magnetic resonance imaging allowed the suspicion of RYR1 as the most likely gene responsible for this myopathy. The diagnosis was subsequently confirmed by the finding of a recessive RYR1 mutation. CONCLUSIONS: The occurrence of congenital myopathy together with cystinuria type B is reported for the first time. The use of muscle magnetic resonance imaging and the homozygosity by descent in SLC7A9, a gene flanking RYR1, allowed us to discover a new mutation in the RYR1 gene.