Myoimaging in the NGS era: the discovery of a novel mutation in MYH7 in a family with distal myopathy and core-like features--a case report

Myosin heavy chain 7 related myopathies are rare disorders characterized by a wide phenotypic spectrum and heterogeneous pathological features. In the present study, we performed clinical, morphological, genetic and imaging investigations in three relatives affected by autosomal dominant distal myopathy. Whilst earlier traditional Sanger investigations had pointed to the wrong gene as disease causative, next-generation sequencing allowed us to obtain the definitive molecular genetic diagnosis in the family

MYH2 myopathy, a new case expands the clinical and pathological spectrum of the recessive form

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Next-generation sequencing approach to hyperCKemia: A 2-year cohort study

Next-generation sequencing (NGS) was applied in molecularly undiagnosed asymptomatic or paucisymptomatic hyperCKemia to investigate whether this technique might allow detection of the genetic basis of the condition

Congenital myopathies: Clinical phenotypes and new diagnostic tools

Congenital myopathies are a group of genetic muscle disorders characterized clinically by hypotonia and weakness, usually from birth, and a static or slowly progressive clinical course. Historically, congenital myopathies have been classified on the basis of major morphological features seen on muscle biopsy. However, different genes have now been identified as associated with the various phenotypic and histological expressions of these disorders, and in recent years, because of their unexpectedly wide genetic and clinical heterogeneity, next-generation sequencing has increasingly been used for their diagnosis. We reviewed clinical and genetic forms of congenital myopathy and defined possible strategies to improve cost-effectiveness in histological and imaging diagnosis

Long-term follow-up in two siblings with pyridoxine-dependent seizures associated with a novel ALDH7A1 mutation.

none7Pyridoxine-dependent seizures (PDS) is a rare disorder characterized by seizures resistant to anticonvulsants but controlled by daily pharmacologic doses of pyridoxine. Mutations in the antiquitin (ALDH7A1) gene have recently reported to cause PDS in most of patients. We report the long-term follow-up in two PDS siblings carrying a novel ALDH7A1 mutation.N. S. Yeghiazaryan;P. Striano;L. Spaccini;M. Pezzella;D. Cassandrini;F. Zara;M. MastrangeloYeghiazaryan, N. S.; Striano, Pasquale; Spaccini, L.; Pezzella, Marianna; Cassandrini, D.; Zara, F.; Mastrangelo, M

Delayed Diagnosis of Glycogen Storage Disease Type III

A case of a delayed diagnosis in adult age of a glycogen storage disease type III is describe

A Diagnostic Dilemma in a Family with Cystinuria Type B Resolved by Muscle Magnetic Resonance

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

Late onset of neutral lipid storage disease due to novel PNPLA2 mutations causing total loss of lipase activity in a patient with myopathy and slight cardiac involvement

Neutral lipid storage disease with myopathy (NLSDM) presents with skeletal muscle myopathy and severe dilated cardiomyopathy in nearly 40% of cases. NLSDM is caused by mutations in the PNPLA2 gene, which encodes the adipose triglyceride lipase (ATGL). Here we report clinical and genetic findings of a patient carrying two novel PNPLA2 mutations (c.696+4A>G and c.553_565delGTCCCCCTTCTCG). She presented at age 39 with right upper limb abduction weakness slowly progressing over the years with asymmetric involvement of proximal upper and lower limb muscles. Cardiological evaluation through ECG and heart echo scan was normal until the age 53, when mild left ventricular diastolic dysfunction was detected. Molecular analysis revealed that only one type of PNPLA2 transcript, with exon 5 skipping, was expressed in patient cells. Such aberrant mRNA causes the production of a shorter ATGL protein, lacking part of the catalytic domain. This is an intriguing case, displaying severe PNPLA2 mutations with clinical presentation characterized by slight cardiac impairment and full expression of severe asymmetric myopathy