Abstract
BackgroundMutations in the PTRF gene, coding for cavin-1, cause congenital generalized lipodystrophy type 4 (CGL4) associated with myopathy. In CGL4, symptoms are variable comprising, in addition to myopathy, smooth and skeletal muscle hypertrophy, cardiac arrhythmias, and skeletal abnormalities. Secondary features are atlantoaxial instability, acanthosis nigricans, hepatomegaly, umbilical prominence and metabolic abnormalities related to insulin resistance, such as diabetes mellitus, hyperlipidemia and hepatic steatosis.Case presentationWe describe a 3 year-old child of Moroccan origin with mild muscle phenotype, mainly characterized by mounding, muscle pain, hyperCKemia and mild caveolin 3 reduction on muscle biopsy. No CAV3 gene mutation was detected; instead we found a novel mutation, a homozygous single base pair deletion, in the PTRF gene. Only after detection of this mutation a mild generalized loss of subcutaneous fat, at first underestimated, was noticed and the diagnosis of lipodystrophy inferred.ConclusionsThe PTRF gene should be investigated in patients with hyperCKemia, mild myopathy associated with spontaneous or percussion-induced muscle contractions like rippling or mounding, and no CAV3 mutation. The analysis should be performed even if cardiac or metabolic alterations are absent, particularly in young patients in whom lipodystrophy may be difficult to ascertain.
Highlights
Mutations in the Polymerase I and transcript release factor (PTRF) gene, coding for cavin-1, cause congenital generalized lipodystrophy type 4 (CGL4) associated with myopathy
The PTRF gene should be investigated in patients with hyperCKemia, mild myopathy associated with spontaneous or percussion-induced muscle contractions like rippling or mounding, and no CAV3 mutation
CGL4 was not diagnosed at first, and the PTRF gene was only investigated because muscle hypertrophy was associated with marked muscle mounding and CAV3 mutations were not found
Summary
Our 3-year-old boy with CGL4 had a mild muscular phenotype mainly characterized by mounding, muscle pain and hyperCKemia. In the presence of myopathy associated with spontaneous or percussion-induced muscle contractions (rippling or mounding), mildly reduced caveolin 3 expression and no CAV3 mutation, the PTRF gene should be investigated, in young patients in whom lipodystrophy may be difficult to ascertain. Alignment of wild type and mutated PTRF gene using ClustalW2 (www.ebi.ac.uk/Tools/msa/clustalw2/). Competing interests The authors declare that they have no competing interests. Authors’ contributions AA, CB, MM, IM conceived and designed the experiments and wrote the manuscript; CB carried out the molecular analysis; FB performed immunochemical evaluation of muscle biopsies and prepared the figures; SM and MLB performed biochemical studies; LM performed muscle biopsy and histological evaluation and critically revised the manuscript; AA, LC and IM performed clinical studies. All authors read and approved the final manuscript
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