A novel pathogenic variant in TNPO3 in a Hungarian family with limb-girdle muscular dystrophy 1F

Care4Rare Canada Consortium

Research output: Contribution to journalArticle

Abstract

Limb-girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous muscular diseases that predominantly affect the proximal muscles. Pathogenic variants in TNPO3 have been associated with a rare, autosomal dominant limb-girdle muscular dystrophy 1F (LGMD1F) in a large Italian-Spanish family and an isolated LGMD1F case. Here we present two individuals from a Hungarian family with an early-onset, slowly progressive muscular dystrophy. Both the female proband and her affected son had delayed early motor milestones including first walking at 14 months and 18 months, respectively. Both present with progressive weakness of facial, bulbar, axial, and distal muscles especially of the lower extremities. Electromyography indicated myogenic damage and muscle biopsy from the proband showed myopathic alterations with sarcoplasmic masses and signs of mitochondrial dysfunction. Exome sequencing of the female proband identified a novel c.2767delC p.(Arg923AspfsTer17) variant in TNPO3. Sanger sequencing confirmed the presence of the TNPO3 variant in the affected son; the unaffected son did not have the variant. The identification of the c.2767delC variant further supports the clinical significance of TNPO3 and expands the clinical spectrum of TNPO3-associated LGMD1F.

Original languageEnglish
Article number103662
JournalEuropean Journal of Medical Genetics
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Limb-Girdle Muscular Dystrophies
Muscles
Exome
Muscular Dystrophies
Electromyography
Muscular Diseases
Walking
Lower Extremity
Biopsy

Keywords

  • Exome sequencing
  • Limb-girdle muscular dystrophy (LGMD)
  • Transportin 3 (TNPO3)

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

A novel pathogenic variant in TNPO3 in a Hungarian family with limb-girdle muscular dystrophy 1F. / Care4Rare Canada Consortium.

In: European Journal of Medical Genetics, 01.01.2019.

Research output: Contribution to journalArticle

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