Disruption of heart sarcoglycan complex and severe cardiomyopathy caused by β sarcoglycan mutations

Rita Barresi, Lucia Morandi, Marina Mora, Claudia Di Blasi, Tiziana Negri, Raffaella Brugnoni, Andrea Vitali, Giorgio Felisari, Antonio Salandi, Sergio Daniel, Ferdinando Cornelio

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Two young males with limb-girdle muscular dystrophy (LGMD) resulting from sarcoglycan deficiency died at 27 (patient 1) and 18 years (patient 2) of severe cardiomyopathy. Genetic analysis showed that they were compound heterozygotes for mutations in the β sarcoglycan gene. One of these mutations, an 8 bp duplication in exon 3, was common to both patients. The second mutation in patient 2 was a 4 bp deletion at the splice donor site of intron 2, not reported previously. Patient 2 had more severe heart and skeletal muscle defects with faster deterioration; no sarcoglycans were detected in his skeletal muscle. The second mutation in patient 1, inferred because the unaffected father carries the 8 bp duplication, was not found. In patient 1, both heart and skeletal muscle were analysed and showed reduction of all sarcoglycans in both tissues and incorrect localisation of α and γ sarcoglycans in heart. Therefore mutations in one sarcoglycan gene can disrupt the entire sarcoglycan complex in both skeletal and cardiac muscle. Differing expression patterns of sarcoglycan components in heart and skeletal muscle could be the result of alternatively spliced transcripts in these tissues. By sequencing an alternative transcript, highly expressed in the heart and skeletal muscle of patient 1, we found an 87 bp cryptic exon not previously reported. Although cardiomyopathy can result from mutations in α and γ sarcoglycans, we show for the first time that the condition can also be caused by mutations in the β sarcoglycan gene. This report therefore expands the phenotype of sarcoglycanopathies and suggests that cardiac function in LGMD patients with defective sarcoglycan expression should be monitored.

Original languageEnglish
Pages (from-to)102-107
Number of pages6
JournalJournal of Medical Genetics
Volume37
Issue number2
Publication statusPublished - 2000

Fingerprint

Sarcoglycans
Cardiomyopathies
Mutation
Skeletal Muscle
Myocardium
Limb-Girdle Muscular Dystrophies
Exons
Sarcoglycanopathies
Genes
RNA Splice Sites
Heterozygote
Fathers
Introns

Keywords

  • Cardiomyopathy
  • Dystrophin associated proteins
  • Limb-girdle muscular dystrophy
  • Sarcoglycans

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Barresi, R., Morandi, L., Mora, M., Di Blasi, C., Negri, T., Brugnoni, R., ... Cornelio, F. (2000). Disruption of heart sarcoglycan complex and severe cardiomyopathy caused by β sarcoglycan mutations. Journal of Medical Genetics, 37(2), 102-107.

Disruption of heart sarcoglycan complex and severe cardiomyopathy caused by β sarcoglycan mutations. / Barresi, Rita; Morandi, Lucia; Mora, Marina; Di Blasi, Claudia; Negri, Tiziana; Brugnoni, Raffaella; Vitali, Andrea; Felisari, Giorgio; Salandi, Antonio; Daniel, Sergio; Cornelio, Ferdinando.

In: Journal of Medical Genetics, Vol. 37, No. 2, 2000, p. 102-107.

Research output: Contribution to journalArticle

Barresi, R, Morandi, L, Mora, M, Di Blasi, C, Negri, T, Brugnoni, R, Vitali, A, Felisari, G, Salandi, A, Daniel, S & Cornelio, F 2000, 'Disruption of heart sarcoglycan complex and severe cardiomyopathy caused by β sarcoglycan mutations', Journal of Medical Genetics, vol. 37, no. 2, pp. 102-107.
Barresi, Rita ; Morandi, Lucia ; Mora, Marina ; Di Blasi, Claudia ; Negri, Tiziana ; Brugnoni, Raffaella ; Vitali, Andrea ; Felisari, Giorgio ; Salandi, Antonio ; Daniel, Sergio ; Cornelio, Ferdinando. / Disruption of heart sarcoglycan complex and severe cardiomyopathy caused by β sarcoglycan mutations. In: Journal of Medical Genetics. 2000 ; Vol. 37, No. 2. pp. 102-107.
@article{88555d906ac044628ec2cbdd85d5bb7d,
title = "Disruption of heart sarcoglycan complex and severe cardiomyopathy caused by β sarcoglycan mutations",
abstract = "Two young males with limb-girdle muscular dystrophy (LGMD) resulting from sarcoglycan deficiency died at 27 (patient 1) and 18 years (patient 2) of severe cardiomyopathy. Genetic analysis showed that they were compound heterozygotes for mutations in the β sarcoglycan gene. One of these mutations, an 8 bp duplication in exon 3, was common to both patients. The second mutation in patient 2 was a 4 bp deletion at the splice donor site of intron 2, not reported previously. Patient 2 had more severe heart and skeletal muscle defects with faster deterioration; no sarcoglycans were detected in his skeletal muscle. The second mutation in patient 1, inferred because the unaffected father carries the 8 bp duplication, was not found. In patient 1, both heart and skeletal muscle were analysed and showed reduction of all sarcoglycans in both tissues and incorrect localisation of α and γ sarcoglycans in heart. Therefore mutations in one sarcoglycan gene can disrupt the entire sarcoglycan complex in both skeletal and cardiac muscle. Differing expression patterns of sarcoglycan components in heart and skeletal muscle could be the result of alternatively spliced transcripts in these tissues. By sequencing an alternative transcript, highly expressed in the heart and skeletal muscle of patient 1, we found an 87 bp cryptic exon not previously reported. Although cardiomyopathy can result from mutations in α and γ sarcoglycans, we show for the first time that the condition can also be caused by mutations in the β sarcoglycan gene. This report therefore expands the phenotype of sarcoglycanopathies and suggests that cardiac function in LGMD patients with defective sarcoglycan expression should be monitored.",
keywords = "Cardiomyopathy, Dystrophin associated proteins, Limb-girdle muscular dystrophy, Sarcoglycans",
author = "Rita Barresi and Lucia Morandi and Marina Mora and {Di Blasi}, Claudia and Tiziana Negri and Raffaella Brugnoni and Andrea Vitali and Giorgio Felisari and Antonio Salandi and Sergio Daniel and Ferdinando Cornelio",
year = "2000",
language = "English",
volume = "37",
pages = "102--107",
journal = "Journal of Medical Genetics",
issn = "0022-2593",
publisher = "BMJ Publishing Group",
number = "2",

}

TY - JOUR

T1 - Disruption of heart sarcoglycan complex and severe cardiomyopathy caused by β sarcoglycan mutations

AU - Barresi, Rita

AU - Morandi, Lucia

AU - Mora, Marina

AU - Di Blasi, Claudia

AU - Negri, Tiziana

AU - Brugnoni, Raffaella

AU - Vitali, Andrea

AU - Felisari, Giorgio

AU - Salandi, Antonio

AU - Daniel, Sergio

AU - Cornelio, Ferdinando

PY - 2000

Y1 - 2000

N2 - Two young males with limb-girdle muscular dystrophy (LGMD) resulting from sarcoglycan deficiency died at 27 (patient 1) and 18 years (patient 2) of severe cardiomyopathy. Genetic analysis showed that they were compound heterozygotes for mutations in the β sarcoglycan gene. One of these mutations, an 8 bp duplication in exon 3, was common to both patients. The second mutation in patient 2 was a 4 bp deletion at the splice donor site of intron 2, not reported previously. Patient 2 had more severe heart and skeletal muscle defects with faster deterioration; no sarcoglycans were detected in his skeletal muscle. The second mutation in patient 1, inferred because the unaffected father carries the 8 bp duplication, was not found. In patient 1, both heart and skeletal muscle were analysed and showed reduction of all sarcoglycans in both tissues and incorrect localisation of α and γ sarcoglycans in heart. Therefore mutations in one sarcoglycan gene can disrupt the entire sarcoglycan complex in both skeletal and cardiac muscle. Differing expression patterns of sarcoglycan components in heart and skeletal muscle could be the result of alternatively spliced transcripts in these tissues. By sequencing an alternative transcript, highly expressed in the heart and skeletal muscle of patient 1, we found an 87 bp cryptic exon not previously reported. Although cardiomyopathy can result from mutations in α and γ sarcoglycans, we show for the first time that the condition can also be caused by mutations in the β sarcoglycan gene. This report therefore expands the phenotype of sarcoglycanopathies and suggests that cardiac function in LGMD patients with defective sarcoglycan expression should be monitored.

AB - Two young males with limb-girdle muscular dystrophy (LGMD) resulting from sarcoglycan deficiency died at 27 (patient 1) and 18 years (patient 2) of severe cardiomyopathy. Genetic analysis showed that they were compound heterozygotes for mutations in the β sarcoglycan gene. One of these mutations, an 8 bp duplication in exon 3, was common to both patients. The second mutation in patient 2 was a 4 bp deletion at the splice donor site of intron 2, not reported previously. Patient 2 had more severe heart and skeletal muscle defects with faster deterioration; no sarcoglycans were detected in his skeletal muscle. The second mutation in patient 1, inferred because the unaffected father carries the 8 bp duplication, was not found. In patient 1, both heart and skeletal muscle were analysed and showed reduction of all sarcoglycans in both tissues and incorrect localisation of α and γ sarcoglycans in heart. Therefore mutations in one sarcoglycan gene can disrupt the entire sarcoglycan complex in both skeletal and cardiac muscle. Differing expression patterns of sarcoglycan components in heart and skeletal muscle could be the result of alternatively spliced transcripts in these tissues. By sequencing an alternative transcript, highly expressed in the heart and skeletal muscle of patient 1, we found an 87 bp cryptic exon not previously reported. Although cardiomyopathy can result from mutations in α and γ sarcoglycans, we show for the first time that the condition can also be caused by mutations in the β sarcoglycan gene. This report therefore expands the phenotype of sarcoglycanopathies and suggests that cardiac function in LGMD patients with defective sarcoglycan expression should be monitored.

KW - Cardiomyopathy

KW - Dystrophin associated proteins

KW - Limb-girdle muscular dystrophy

KW - Sarcoglycans

UR - http://www.scopus.com/inward/record.url?scp=0034063935&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034063935&partnerID=8YFLogxK

M3 - Article

C2 - 10662809

AN - SCOPUS:0034063935

VL - 37

SP - 102

EP - 107

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

IS - 2

ER -