Exome sequencing identifies a novel mutation in PIK3R1 as the cause of SHORT syndrome
1 Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain
2 Aix-Marseille Université, Inserm UMR_S 910, Faculté de Médecine de Marseille, 13385 Marseille cedex 05, France
3 AP-HM, Département de Génétique Médicale, Hôpital d’Enfants de la Timone, 13385 Marseille cedex 05, France
4 Departamento de Genética, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain
5 Cardiology and Cardiosurgical Department, Bambino Gesú Children’s Hospital, 00165 Rome, Italy
BMC Medical Genetics 2014, 15:51 doi:10.1186/1471-2350-15-51Published: 2 May 2014
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.
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.
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.