Phenotypic Spectrum of Myopathies with Recessive Anoctamin-5 Mutations
| العنوان: | Phenotypic Spectrum of Myopathies with Recessive Anoctamin-5 Mutations |
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| المؤلفون: | José Vázquez, Claire Lefeuvre, Rosa Elena Escobar, Alexandra Berenice Luna Angulo, Antonio Miranda Duarte, Alma Delia Hernandez, Marion Brisset, Robert-Yves Carlier, France Leturcq, Marie-Christine Durand-Canard, Guillaume Nicolas, Pascal Laforet, Edoardo Malfatti |
| المصدر: | Journal of Neuromuscular Diseases. 7:443-451 |
| بيانات النشر: | IOS Press, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adult, 0301 basic medicine, Pathology, medicine.medical_specialty, Anoctamins, Compound heterozygosity, Asymptomatic, Pulmonary function testing, Cohort Studies, Manual Muscle Testing, 03 medical and health sciences, Exon, 0302 clinical medicine, Muscular Diseases, Humans, Medicine, Muscular dystrophy, Myopathy, Creatine Kinase, Mexico, Muscle Weakness, Muscle biopsy, medicine.diagnostic_test, business.industry, Myalgia, medicine.disease, Pedigree, Distal Myopathies, Muscular Atrophy, 030104 developmental biology, Muscular Dystrophies, Limb-Girdle, Neurology, Mutation, France, Neurology (clinical), medicine.symptom, business, Metabolism, Inborn Errors, 030217 neurology & neurosurgery |
| الوصف: | Background: Biallelic variants in Anoctamin 5 (ANO5) gene are causative of limb-girdle muscular dystrophy (LGMD) R12 anoctamin5-related, non-dysferlin Miyoshi-like distal myopathy (MMD3), and asymptomatic hyperCKemia. Objective: To describe clinic, histologic, genetic and imaging features, of ANO5 mutated patients. Methods: Five patients, four from France (P1, P2, P3 and P4) and one from Mexico (P5), from four families were included. P1 and P2, belonging to group 1, had normal muscle strength; Group 2, P3, P4 and P5, presented with muscular weakness. Muscle strength was measured by manual muscle testing, Medical Research Council (MRC) grades 1/5 to 5/5. Laboratory exams included serum CK levels, nerve conduction studies (NCS)/needle electromyography (EMG), pulmonary function tests, EKG and cardiac ultrasound. ANO5 molecular screening was performed with different approaches. Results: Group 1 patients showed myalgias with hyperCKemia or isolated hyperCKemia. Group 2 patients presented with limb-girdle or proximo-distal muscular weakness. Serum CK levels ranged from 897 to 5000 UI/L. Muscle biopsy analysis in P4 and P5 showed subsarcolemmal mitochondrial aggregates. Electron microscopy confirmed mitochondrial proliferation and revealed discontinuity of the sarcolemmal membrane. Muscle MRI showed asymmetrical fibro-fatty substitution predominant in the lower limbs. P1 and P2 were compound heterozygous for c.191dupA (p.Asn64Lysfs*15) and c.1898 + G>A; P3 was homozygous for the c.692G>T. (p.Gly231Val); P4 harbored a novel biallelic homozygous exons 1–7 ANO5 gene deletion, and P5 was homozygous for a c.172 C > T (p.(Arg 58 Trp)) ANO5 pathogenic variant. Conclusions: Our cohort confirms the wide clinical variability and enlarge the genetic spectrum of ANO5-related myopathies. |
| تدمد: | 2214-3602 2214-3599 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c18d7cf55dcf61d9e572ab7dbf28b1caTest https://doi.org/10.3233/jnd-200515Test |
| رقم الانضمام: | edsair.doi.dedup.....c18d7cf55dcf61d9e572ab7dbf28b1ca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22143602 22143599 |
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