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

TITLE=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

JOURNAL=Frontiers in Genetics

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.565868

DOI=10.3389/fgene.2020.565868

ISSN=1664-8021

ABSTRACT=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 to 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.