title: Exome sequencing identifies a novel mutation in PIK3R1 as the cause of SHORT syndrome.
abstract: BACKGROUND
  SHORT syndrome is a rare autosomal dominant condition whose name is the acronym of short stature, hyperextensibility of joints, ocular depression, Rieger anomaly and teething delay (MIM 269880). Additionally, the patients usually present a low birth weight and height, lipodystrophy, delayed bone age, hernias, low body mass index and a progeroid appearance.
  
  
  METHODS
  In this study, we used whole-exome sequencing approaches in two patients with clinical features of SHORT syndrome. We report the finding of a novel mutation in PIK3R1 (c.1929_1933delTGGCA; p.Asp643Aspfs*8), as well as a recurrent mutation c.1945C > T (p.Arg649Trp) in this gene.
  
  
  CONCLUSIONS
  We found a novel frameshift mutation in PIK3R1 (c.1929_1933delTGGCA; p.Asp643Aspfs*8) which consists of a deletion right before the site of substrate recognition. As a consequence, the protein lacks the position that interacts with the phosphotyrosine residue of the substrate, resulting in the development of SHORT syndrome.
authors.forename: Clea
authors.initials: C
authors.lastname: Bárcena
authors.forename: Víctor
authors.initials: V
authors.lastname: Quesada
authors.forename: Annachiara
authors.initials: A
authors.lastname: De Sandre-Giovannoli
authors.forename: Diana A
authors.initials: DA
authors.lastname: Puente
authors.forename: Joaquín
authors.initials: J
authors.lastname: Fernández-Toral
authors.forename: Sabine
authors.initials: S
authors.lastname: Sigaudy
authors.forename: Anwar
authors.initials: A
authors.lastname: Baban
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lévy
authors.forename: Gloria
authors.initials: G
authors.lastname: Velasco
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain. clo@uniovi.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Otín
mesh_terms: D019943:Amino Acid Substitution; D002675:Child, Preschool; D058543:Class Ia Phosphatidylinositol 3-Kinase; D004252:DNA Mutational Analysis; D059472:Exome; D019066:Facies; D006130:Growth Disorders / Q000175:diagnosis* / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D006934:Hypercalcemia / Q000175:diagnosis* / Q000235:genetics*; D007223:Infant; D008297:Male; D008659:Metabolic Diseases / Q000175:diagnosis* / Q000235:genetics*; D008958:Models, Molecular; D009154:Mutation; D009397:Nephrocalcinosis / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000235:genetics*; D011487:Protein Conformation
chemical_list: D058543:Class Ia Phosphatidylinositol 3-Kinase; D019869:Phosphatidylinositol 3-Kinases; C588001:PIK3R1 protein, human