Frequency and characterisation of anoctamin 5 mutations in a cohort of Italian limb-girdle muscular dystrophy patients

Francesca Magri, Roberto Del Bo, Maria Grazia D'Angelo, Monica Sciacco, Sandra Gandossini, Alessandra Govoni, Laura Napoli, Patrizia Ciscato, Francesco Fortunato, Erika Brighina, Sara Bonato, Andreina Bordoni, Valeria Lucchini, Stefania Corti, Maurizio Moggio, Nereo Bresolin, Giacomo Pietro Comi

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Abstract

Limb-girdle muscular dystrophy (LGMD) 2L, caused by mutations in the anoctamin 5 (ANO5) gene, is the third most common LGMD in Northern and Central Europe, where the c.191dupA mutation causes the majority of cases. We evaluated data from 228 Italian LGMD patients to determine the prevalence of LGMD2L and the c.191dupA mutation, and to describe the clinical, muscle biopsy, and magnetic resonance imaging findings in these patients. Forty-three patients who lacked molecular diagnosis were studied for ANO5 mutations, and four novel mutations were found in three probands. Only one proband carried the c.191dupA mutation, which was compound heterozygous with c.2516T>G. Two probands were homozygous for the c.1627dupA and c.397A>T mutations, respectively, while a fourth proband had a compound heterozygous status (c.220C>T and c.1609T>C). Therefore occurrence and molecular epidemiology of LGMD2L in this Italian cohort differed from those observed in other European countries. ANO5 mutations accounted for ∼2% of our sample. Affected patients exhibited benign progression with variable onset and an absence of cardiac and respiratory impairment; muscle biopsy generally showed mild signs, except when performed on the quadriceps muscles; MRI showed predominant involvement of the posterior thigh. Overall these common clinical, morphological and imaging findings could be useful in differential diagnosis.

Original languageEnglish
Pages (from-to)934-943
Number of pages10
JournalNeuromuscular Disorders
Volume22
Issue number11
DOIs
Publication statusPublished - Nov 2012

Fingerprint

Limb-Girdle Muscular Dystrophies
Mutation
Biopsy
Muscles
Molecular Epidemiology
Quadriceps Muscle
Thigh
Differential Diagnosis
Magnetic Resonance Imaging

Keywords

  • Anoctamin 5
  • Chloride channel
  • Limb girdle muscular dystrophy 2L
  • Membrane repair
  • Quadriceps myopathy

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)
  • Neurology

Cite this

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title = "Frequency and characterisation of anoctamin 5 mutations in a cohort of Italian limb-girdle muscular dystrophy patients",
abstract = "Limb-girdle muscular dystrophy (LGMD) 2L, caused by mutations in the anoctamin 5 (ANO5) gene, is the third most common LGMD in Northern and Central Europe, where the c.191dupA mutation causes the majority of cases. We evaluated data from 228 Italian LGMD patients to determine the prevalence of LGMD2L and the c.191dupA mutation, and to describe the clinical, muscle biopsy, and magnetic resonance imaging findings in these patients. Forty-three patients who lacked molecular diagnosis were studied for ANO5 mutations, and four novel mutations were found in three probands. Only one proband carried the c.191dupA mutation, which was compound heterozygous with c.2516T>G. Two probands were homozygous for the c.1627dupA and c.397A>T mutations, respectively, while a fourth proband had a compound heterozygous status (c.220C>T and c.1609T>C). Therefore occurrence and molecular epidemiology of LGMD2L in this Italian cohort differed from those observed in other European countries. ANO5 mutations accounted for ∼2{\%} of our sample. Affected patients exhibited benign progression with variable onset and an absence of cardiac and respiratory impairment; muscle biopsy generally showed mild signs, except when performed on the quadriceps muscles; MRI showed predominant involvement of the posterior thigh. Overall these common clinical, morphological and imaging findings could be useful in differential diagnosis.",
keywords = "Anoctamin 5, Chloride channel, Limb girdle muscular dystrophy 2L, Membrane repair, Quadriceps myopathy",
author = "Francesca Magri and Bo, {Roberto Del} and D'Angelo, {Maria Grazia} and Monica Sciacco and Sandra Gandossini and Alessandra Govoni and Laura Napoli and Patrizia Ciscato and Francesco Fortunato and Erika Brighina and Sara Bonato and Andreina Bordoni and Valeria Lucchini and Stefania Corti and Maurizio Moggio and Nereo Bresolin and Comi, {Giacomo Pietro}",
year = "2012",
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doi = "10.1016/j.nmd.2012.05.001",
language = "English",
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T1 - Frequency and characterisation of anoctamin 5 mutations in a cohort of Italian limb-girdle muscular dystrophy patients

AU - Magri, Francesca

AU - Bo, Roberto Del

AU - D'Angelo, Maria Grazia

AU - Sciacco, Monica

AU - Gandossini, Sandra

AU - Govoni, Alessandra

AU - Napoli, Laura

AU - Ciscato, Patrizia

AU - Fortunato, Francesco

AU - Brighina, Erika

AU - Bonato, Sara

AU - Bordoni, Andreina

AU - Lucchini, Valeria

AU - Corti, Stefania

AU - Moggio, Maurizio

AU - Bresolin, Nereo

AU - Comi, Giacomo Pietro

PY - 2012/11

Y1 - 2012/11

N2 - Limb-girdle muscular dystrophy (LGMD) 2L, caused by mutations in the anoctamin 5 (ANO5) gene, is the third most common LGMD in Northern and Central Europe, where the c.191dupA mutation causes the majority of cases. We evaluated data from 228 Italian LGMD patients to determine the prevalence of LGMD2L and the c.191dupA mutation, and to describe the clinical, muscle biopsy, and magnetic resonance imaging findings in these patients. Forty-three patients who lacked molecular diagnosis were studied for ANO5 mutations, and four novel mutations were found in three probands. Only one proband carried the c.191dupA mutation, which was compound heterozygous with c.2516T>G. Two probands were homozygous for the c.1627dupA and c.397A>T mutations, respectively, while a fourth proband had a compound heterozygous status (c.220C>T and c.1609T>C). Therefore occurrence and molecular epidemiology of LGMD2L in this Italian cohort differed from those observed in other European countries. ANO5 mutations accounted for ∼2% of our sample. Affected patients exhibited benign progression with variable onset and an absence of cardiac and respiratory impairment; muscle biopsy generally showed mild signs, except when performed on the quadriceps muscles; MRI showed predominant involvement of the posterior thigh. Overall these common clinical, morphological and imaging findings could be useful in differential diagnosis.

AB - Limb-girdle muscular dystrophy (LGMD) 2L, caused by mutations in the anoctamin 5 (ANO5) gene, is the third most common LGMD in Northern and Central Europe, where the c.191dupA mutation causes the majority of cases. We evaluated data from 228 Italian LGMD patients to determine the prevalence of LGMD2L and the c.191dupA mutation, and to describe the clinical, muscle biopsy, and magnetic resonance imaging findings in these patients. Forty-three patients who lacked molecular diagnosis were studied for ANO5 mutations, and four novel mutations were found in three probands. Only one proband carried the c.191dupA mutation, which was compound heterozygous with c.2516T>G. Two probands were homozygous for the c.1627dupA and c.397A>T mutations, respectively, while a fourth proband had a compound heterozygous status (c.220C>T and c.1609T>C). Therefore occurrence and molecular epidemiology of LGMD2L in this Italian cohort differed from those observed in other European countries. ANO5 mutations accounted for ∼2% of our sample. Affected patients exhibited benign progression with variable onset and an absence of cardiac and respiratory impairment; muscle biopsy generally showed mild signs, except when performed on the quadriceps muscles; MRI showed predominant involvement of the posterior thigh. Overall these common clinical, morphological and imaging findings could be useful in differential diagnosis.

KW - Anoctamin 5

KW - Chloride channel

KW - Limb girdle muscular dystrophy 2L

KW - Membrane repair

KW - Quadriceps myopathy

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