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

C Bárcena, V Quesada, A De Sandre-Giovannoli… - BMC medical …, 2014 - Springer
C Bárcena, V Quesada, A De Sandre-Giovannoli, DA Puente, J Fernández-Toral, S Sigaudy…
BMC medical genetics, 2014Springer
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 …
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.
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