A single c.1715G>C calpain 3 gene variant causes dominant calpainopathy with loss of calpain 3 expression and activity

Autor: Thomas Krag, Carinne Roudaut, John Vissing, Julia R. Dahlqvist, Morten Duno, Isabelle Richard, Jerome Poupiot
Přispěvatelé: University of Copenhagen = Københavns Universitet (KU), Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, University of Copenhagen = Københavns Universitet (UCPH), Richard, Isabelle
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Adult
Male
Proband
[SDV.BIO]Life Sciences [q-bio]/Biotechnology
Adolescent
Muscle Proteins
calpain 3
[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
medicine.disease_cause
Young Adult
03 medical and health sciences
Genetics
medicine
Humans
Missense mutation
Child
Genetics (clinical)
limb girdle muscular dystrophy
Aged
030304 developmental biology
0303 health sciences
Mutation
Muscle biopsy
dominant inheritance
biology
medicine.diagnostic_test
Calpain
030305 genetics & heredity
Muscle weakness
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
Middle Aged
medicine.disease
Molecular biology
Pedigree
[SDV.BIO] Life Sciences [q-bio]/Biotechnology
calpainopathy
Muscular Dystrophies
Limb-Girdle
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
biology.protein
Creatine kinase
medicine.symptom
Limb-girdle muscular dystrophy
Zdroj: Human Mutation
Human Mutation, Wiley, 2020, 41 (9), pp.1507-1513. ⟨10.1002/humu.24066⟩
Human Mutation, 2020, 41 (9), pp.1507-1513. ⟨10.1002/humu.24066⟩
ISSN: 1059-7794
1098-1004
Popis: Recessively inherited limb girdle muscular dystrophy (LGMD) type 2A is the most common LGMD worldwide. Here, we report the first single missense variant in CAPN3 causing dominantly inherited calpainopathy. A 43-year-old proband, his father and two sons were heterozygous for a c.1715G>C p.(Arg572Pro) variant in CAPN3. Affected family members had at least three of the following; muscle pain, a LGMD2A pattern of muscle weakness and wasting, muscle fat replacement on MRI, myopathic muscle biopsy, and elevated creatine kinase. Total calpain 3 protein expression was 4 ± 3% of normal. In vitro analysis of c.1715G>C and the previously described c.643_663del variant indicated that the mutant proteins lack autolytic and proteolytic activity and decrease the quantity of wild-type CAPN3 protein. Our findings suggest that dominantly inherited calpainopathy is not unique to the previously reported c.643_663del mutation of CAPN3, and that dominantly inherited calpainopathy should be considered for other single variations in CAPN3. This article is protected by copyright. All rights reserved.
Databáze: OpenAIRE
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