title: PIK3R1 mutations in SHORT syndrome.
abstract: SHORT syndrome (OMIM 269880) is a rare autosomal-dominant disorder characterized by short stature, hyperextensibility of joints, hernias, ocular depression, ophthalmic anomalies (Rieger anomaly, posterior embryotoxon, glaucoma), teething delay, partial lipodystrophy, insulin resistance and facial dysmorphic signs. Heterozygous mutations in PIK3R1 were recently identified in 14 families with SHORT syndrome. Eight of these families had a recurrent missense mutation (c.1945C>T; p.Arg649Trp). We report on two unrelated patients with typical clinical features of SHORT syndrome and additional problems such as pulmonary stenosis and ectopic kidney. Analysis of PIK3R1 revealed the mutation c.1945C>T; p.Arg649Trp de novo in both patients. These two patients not only provide additional evidence that PIK3R1 mutations cause SHORT syndrome, but also broaden the clinical spectrum of this syndrome and further confirm that the amino acid exchange c.1945C>T; p.Arg649Trp is a hotspot mutation in this gene.
authors: Institute of Medical Genetics and Applied Genomics.
authors: C
authors: C
authors: Schroeder
authors: A
authors: A
authors: Riess
authors: M
authors: M
authors: Bonin
authors: P
authors: P
authors: Bauer
authors: O
authors: O
authors: Riess
authors: M
authors: M
authors: Döbler-Neumann
authors: S
authors: S
authors: Wieser
authors: U
authors: U
authors: Moog
authors: A
authors: A
authors: Tzschach
mesh_terms: D058543:Class Ia Phosphatidylinositol 3-Kinase; D017931:DNA Primers / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006130:Growth Disorders / Q000235:genetics* / Q000473:pathology*; D006579:Heterozygote; D006801:Humans; D006934:Hypercalcemia / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008659:Metabolic Diseases / Q000235:genetics* / Q000473:pathology*; D020125:Mutation, Missense / Q000235:genetics; D009397:Nephrocalcinosis / Q000235:genetics* / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D058543:Class Ia Phosphatidylinositol 3-Kinase; D017931:DNA Primers; D019869:Phosphatidylinositol 3-Kinases; C588001:PIK3R1 protein, human
keywords: PIK3R1; Rieger anomaly; SHORT syndrome; ectopic kidney; lipodystrophy; pulmonary stenosis; short stature