Frontiers in Genetics (2020-09-01)

A Recurrent Pathogenic Variant of INPP5K Underlies Autosomal Recessive Congenital Muscular Dystrophy With Cataracts and Intellectual Disability: Evidence for a Founder Effect in Southern Italy

  • Adele D’Amico,
  • Adele D’Amico,
  • Fabiana Fattori,
  • Fabiana Fattori,
  • Francesco Nicita,
  • Francesco Nicita,
  • Sabina Barresi,
  • Giorgio Tasca,
  • Margherita Verardo,
  • Simone Pizzi,
  • Isabella Moroni,
  • Francesca De Mitri,
  • Annalia Frongia,
  • Marika Pane,
  • Eugenio Mercuri,
  • Marco Tartaglia,
  • Enrico Bertini,
  • Enrico Bertini

Journal volume & issue
Vol. 11


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Inositol polyphosphate-5-phosphatase K [INPP5K (MIM: 607875)] acts as a PIP3 5-phosphatase and regulates actin cytoskeleton, insulin, and cell migration. Biallelic pathogenic variants in INPP5K have recently been reported in patients affected by a form of muscular dystrophy with childhood onset. Affected patients have limb girdle muscle weakness, often associated with bilateral cataracts, short stature, and intellectual disability. Here we report four patients affected by INPP5K-related muscle dystrophy, who were apparently unrelated but originated from the same geographical area in South Italy. These patients manifest a recognizable phenotype characterized by early onset muscular dystrophy associated with short stature and intellectual disability. All affected subjects were homozygous or compound heterozygous for the c.67G > A (p.Val23Met) missense change and shared a common haplotype, indicating the occurrence of a founder effect.