A new case of limb girdle muscular dystrophy 2G in a Greek patient, founder effect and review of the literature

Roberta Brusa, Francesca Magri, Dimitra Papadimitriou, Alessandra Govoni, Roberto Del Bo, Patrizia Ciscato, Marco Savarese, Claudia Cinnante, Maggie C. Walter, Angela Abicht, Stefanie Bulst, Stefania Corti, Maurizio Moggio, Nereo Bresolin, Vincenzo Nigro, Giacomo Pietro Comi

Research output: Contribution to journalArticle

Abstract

Limb girdle muscular dystrophy (LGMD) type 2G is a rare form of muscle disease, described only in a few patients worldwide, caused by mutations in TCAP gene, encoding the protein telethonin. It is characterised by proximal limb muscle weakness associated with distal involvement of lower limbs, starting in the first or second decade of life. We describe the case of a 37-year-old woman of Greek origin, affected by disto-proximal lower limb weakness. No cardiac or respiratory involvement was detected. Muscle biopsy showed myopathic changes with type I fibre hypotrophy, cytoplasmic vacuoles, lipid overload, multiple central nuclei and fibre splittings; ultrastructural examination showed metabolic abnormalities. Next generation sequencing analysis detected a homozygous frameshift mutation in the TCAP gene (c.90_91del), previously described in one Turkish family. Immunostaining and Western blot analysis showed complete absence of telethonin. Interestingly, Single Nucleotide Polymorphism analysis of the 10 Mb genomic region containing the TCAP gene showed a shared homozygous haplotype of both the Greek and the Turkish patients, thus suggesting a possible founder effect of TCAP gene c.90_91del mutation in this part of the Mediterranean area.

Original languageEnglish
Pages (from-to)532-537
JournalNeuromuscular Disorders
Volume28
Issue number6
DOIs
Publication statusPublished - 2018

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Keywords

  • Founder effect
  • Limb girdle muscular dystrophy 2G
  • TCAP gene
  • Telethonin

ASJC Scopus subject areas

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

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