Abstract:
:Brody disease is an inherited myopathy associated with a defective function of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 1 (SERCA1) protein. Mutations in the ATP2A1 gene have been reported only in some patients. Therefore it has been proposed to distinguish patients with ATP2A1 mutations, Brody disease (BD), from patients without mutations, Brody syndrome (BS). We performed a detailed study of SERCA1 protein expression in muscle of patients with BD and BS, and evaluated the alternative splicing of SERCA1 in primary cultures of normal human muscle and in infant muscle. SERCA1 reactivity was observed in type 2 muscle fibers of patients with and without ATP2A1 mutations and staining intensity was similar in patients and controls. Immunoblot analysis showed a significant reduction of SERCA1 band in muscle of BD patients. In addition we demonstrated that the wild type and mutated protein exhibits similar solubility properties and that RIPA buffer improves the recovery of the wild type and mutated SERCA1 protein. We found that SERCA1b, the SERCA1 neonatal form, is the main protein isoform expressed in cultured human muscle fibers and infant muscle. Finally, we identified two novel heterozygous mutations within exon 3 of the ATP2A1 gene from a previously described patient with BD.
journal_name
Mol Genet Metabjournal_title
Molecular genetics and metabolismauthors
Guglielmi V,Vattemi G,Gualandi F,Voermans NC,Marini M,Scotton C,Pegoraro E,Oosterhof A,Kósa M,Zádor E,Valente EM,De Grandis D,Neri M,Codemo V,Novelli A,van Kuppevelt TH,Dallapiccola B,van Engelen BG,Ferlini A,Tomelldoi
10.1016/j.ymgme.2013.07.015subject
Has Abstractpub_date
2013-09-01 00:00:00pages
162-9issue
1-2eissn
1096-7192issn
1096-7206pii
S1096-7192(13)00261-8journal_volume
110pub_type
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