Exome sequencing identifies a novel mutation in PIK3R1 as the cause of SHORT syndrome

BMC Medical Genetics

Carlos López-Otín²  Gloria Velasco²  Nicolas Lévy⁴  Anwar Baban³  Sabine Sigaudy⁴  Joaquín Fernández-Toral¹  Diana A Puente²  Annachiara De Sandre-Giovannoli⁴  Víctor Quesada²  Clea Bárcena² 

[1] Departamento de Genética, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain;Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain;Cardiology and Cardiosurgical Department, Bambino Gesú Children’s Hospital, 00165 Rome, Italy;AP-HM, Département de Génétique Médicale, Hôpital d’Enfants de la Timone, 13385 Marseille cedex 05, France

关键词: Progeria;    Lipodystrophy;    Kinase;    Insulin;    Diabetes;    Aging;   

Others  :  1091921
DOI  :  10.1186/1471-2350-15-51

 received in 2013-11-08, accepted in 2014-04-25,  发布年份 2014

【 摘 要 】

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.

Case presentation

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.

【 授权许可】

   
2014 Bárcena et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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