Entire CAPN3 gene deletion in a patient with limb-girdle muscular dystrophy type 2A

2014 ◽  
Vol 50 (3) ◽  
pp. 448-453 ◽  
Author(s):  
Oihane Jaka ◽  
Margarita Azpitarte ◽  
Coro Paisán-Ruiz ◽  
Miren Zulaika ◽  
Leire Casas-Fraile ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Gene Deletion ◽  
Limb Girdle Muscular Dystrophy ◽  
Capn3 Gene

P.P.6 03 Incidence of 550delA in the CAPN3 gene in German patients with limb-girdle muscular dystrophy and hyperCKemia

2006 ◽  
Vol 16 (9-10) ◽  
pp. 694-695 ◽  
Author(s):  
F. Hanisch ◽  
D. Grimm ◽  
L. Xue ◽  
C. Müller-Reible ◽  
S. Zierz ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Limb Girdle Muscular Dystrophy ◽  
Capn3 Gene

scholarly journals Limb-girdle muscular dystrophy type 2A in Brazilian children

2015 ◽  
Vol 73 (12) ◽  
pp. 993-997 ◽  
Author(s):  
Marco Antônio Veloso de Albuquerque ◽  
Osório Abath Neto ◽  
Francisco Marcos Alencar da Silva ◽  
Edmar Zanoteli ◽  
Umbertina Conti Reed
Keyword(s):  
Muscular Dystrophy ◽  
Disease Onset ◽  
Limb Girdle Muscular Dystrophy ◽  
Lower Limbs ◽  
Clinical Aspects ◽  
Mri Findings ◽  
Muscle Mri ◽  
Scapular Winging ◽  
Muscle Biopsies ◽  
Capn3 Gene

ABSTRACT Calpainopathy is an autosomal recessive limb girdle muscular dystrophy (LGMD2A) caused by mutations in CAPN3 gene. Objective To present clinical and histological findings in six children with a molecular diagnosis of LGMD2A and additionally the MRI findings in two of them. Method We retrospectively assessed medical records of 6 patients with mutation on CAPN3 gene. Results All patients were female (three to 12 years). The mean of age of disease onset was 9 years. All of them showed progressive weakness with predominance in lower limbs. Other findings were scapular winging, joint contractures and calf hypertrophy. One female had a more severe phenotype than her dizygotic twin sister that was confirmed by muscle MRI. Muscle biopsies showed a dystrophic pattern in all patients. Conclusion In this cohort of children with LGMD2A, the clinical aspects were similar to adults with the same disorder.

scholarly journals A case of pseudodominant inheritance of limb-girdle muscular dystrophy caused by mutations in the CAPN3 gene

2021 ◽  
Vol 15 (3) ◽  
pp. 85-91
Author(s):  
Inna V. Sharkova ◽  
Maria V. Bulakh ◽  
Liudmila А. Bessonova ◽  
Olga A. Shchagina ◽  
Elena L. Dadaly
Keyword(s):  
Muscular Dystrophy ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Disease Onset ◽  
Limb Girdle Muscular Dystrophy ◽  
Compound Heterozygous ◽  
Carrier Status ◽  
Heterozygous Carrier ◽  
Calpain 3 ◽  
Capn3 Gene

Introduction. Limb-girdle muscular dystrophy (LGMD) includes more than 30 forms caused by mutations in genes located on autosomes. The most common form is calpain-3-related LGMD, with autosomal recessive inheritance pattern (OMIM 253600). An autosomal dominant form of LGMD (OMIM 618129) caused by c.643_663del heterozygous mutation in the CAPN3 gene is also supposed to exist. This article describes a family case of LGMD caused by mutations in the CAPN3 gene with pseudodominant inheritance. Materials and methods. Two patients with LGMD were studied: a 59-year-old woman and her 38-year-old daughter. Clinical, genealogical and molecular genetics methods were used: limb girdle muscular dystrophy MPS panel, Sanger sequencing of DNA of the proband, her affected daughter, and six first- and second-degree relatives across four generations. Results. It was found that identical variants of the nucleotide sequence, c.598_612del and c.1746-20CG, identified in the CAPN3 gene of the proband and her daughter, are in the trans position (compound heterozygous state), causing autosomal recessive calpain-3-related LGMD. This is an example of an incredibly rare pseudodominant inheritance of an autosomal recessive disease, established through indirect evidence that the probands husband is a heterozygous carrier of a nucleotide substitution in the CAPN3 gene. Conclusion. It is crucial to examine the marriage partner for heterozygous carrier status of a gene mutation responsible for the disease in family planning and when clarifying the childs prognosis for a patient with an autosomal recessive disease. Considering the existence of a late-onset (after 30 years) LGMD phenotype associated with the CAPN3 gene, differential diagnosis should begin with testing this gene in families with late disease onset.

scholarly journals Calcium Mechanisms in Limb-Girdle Muscular Dystrophy with CAPN3 Mutations

2019 ◽  
Vol 20 (18) ◽  
pp. 4548 ◽  
Author(s):  
Jaione Lasa-Elgarresta ◽  
Laura Mosqueira-Martín ◽  
Neia Naldaiz-Gastesi ◽  
Amets Sáenz ◽  
Adolfo López de Munain ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Inclusion Body Myositis ◽  
Disease Onset ◽  
Therapeutic Strategies ◽  
Limb Girdle Muscular Dystrophy ◽  
Sporadic Inclusion Body Myositis ◽  
Children And Young Adults ◽  
Novel Approaches ◽  
Progressive Weakness ◽  
Capn3 Gene

Limb-girdle muscular dystrophy recessive 1 (LGMDR1), previously known as LGMD2A, is a rare disease caused by mutations in the CAPN3 gene. It is characterized by progressive weakness of shoulder, pelvic, and proximal limb muscles that usually appears in children and young adults and results in loss of ambulation within 20 years after disease onset in most patients. The pathophysiological mechanisms involved in LGMDR1 remain mostly unknown, and to date, there is no effective treatment for this disease. Here, we review clinical and experimental evidence suggesting that dysregulation of Ca2+ homeostasis in the skeletal muscle is a significant underlying event in this muscular dystrophy. We also review and discuss specific clinical features of LGMDR1, CAPN3 functions, novel putative targets for therapeutic strategies, and current approaches aiming to treat LGMDR1. These novel approaches may be clinically relevant not only for LGMDR1 but also for other muscular dystrophies with secondary calpainopathy or with abnormal Ca2+ homeostasis, such as LGMD2B/LGMDR2 or sporadic inclusion body myositis.

scholarly journals Limb-girdle muscular dystrophy in the Agarwals: Utility of founder mutations in CAPN3 gene

2016 ◽  
Vol 19 (1) ◽  
pp. 108 ◽  
Author(s):  
SatishV Khadilkar ◽  
ChetanR Chaudhari ◽  
RashnaS Dastur ◽  
PradnyaS Gaitonde ◽  
JayendraG Yadav
Keyword(s):  
Muscular Dystrophy ◽  
Limb Girdle Muscular Dystrophy ◽  
Founder Mutations ◽  
Capn3 Gene

scholarly journals Allosteric Modulation of GSK-3β as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related

2021 ◽  
Vol 22 (14) ◽  
pp. 7367
Author(s):  
Anabel Rico ◽  
Garazi Guembelzu ◽  
Valle Palomo ◽  
Ana Martínez ◽  
Ana Aiastui ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Autosomal Recessive ◽  
Glycogen Synthase ◽  
Limb Girdle Muscular Dystrophy ◽  
Pathophysiological Mechanism ◽  
Calpain 3 ◽  
Competitive Inhibitors ◽  
Gsk 3Β ◽  
Muscle Homeostasis ◽  
Capn3 Gene

Limb-girdle muscular dystrophy R1 calpain 3-related (LGMDR1) is an autosomal recessive muscular dystrophy produced by mutations in the CAPN3 gene. It is a rare disease and there is no cure or treatment for the disease while the pathophysiological mechanism by which the absence of calpain 3 provokes the dystrophy in muscles is not clear. However, key proteins implicated in Wnt and mTOR signaling pathways, which regulate muscle homeostasis, showed a considerable reduction in their expression and in their phosphorylation in LGMDR1 patients’ muscles. Finally, the administration of tideglusib and VP0.7, ATP non-competitive inhibitors of glycogen synthase kinase 3β (GSK-3β), restore the expression and phosphorylation of these proteins in LGMDR1 cells, opening the possibility of their use as therapeutic options.

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