Variant PIK3R1 Hypermorphic Mutation and Clinical Phenotypes in a Family with Short Statures, Mild Immunodeficiency and Lymphoma

Abstract

Background Heterozygous point mutations in the GT splice donor consensus sequence of exon 11 of the PIK3R1 gene (coding for p85α, p55α, and p50α regulatory subunits of PI3K) lead to exon skipping and thereby to an aberrant protein that leaves PI3K hyperactivated. Several patients with this particular variant of PI3 kinase delta syndrome (APDS) suffering from sinopulmonary infections and lymphoproliferation have been described.

Methods (Whole exome) sequencing, evaluation of cellular and clinical phenotypes.

Results We here report a family with a new heterozygous mutation in this gene, a 9 bp deletion (c.1418_1425+1del) that, however, leads to the same skipping of exon 11. The clinical phenotypes of their members partly overlap features of patients of other reports.

Conclusions We found a new mutation in PIK3R1 and show how broad the resulting clinical spectrum can be.

Zusammenfassung

Hintergrund Heterozygote Punktmutationen in der GT Spleißdonorsequenz von Exon 11 des PIK3R1 Gens (codiert die regulatorischen Untereinheiten p85α, p55α, und p50α von PI3K) führen zu Exonskipping und dadurch zu einem abweichenden hyperaktiven PI3K Protein. Mehrere Patienten mit dieser speziellen Variante des PI3 Kinase Delta Syndroms (APDS), die unter sinopulmonalen Infektionen und Lymphoproliferation litten, wurden beschrieben.

Methoden (Ganzexom-) Sequenzierung, Bestimmung der zellulären und klinischen Phänotypen.

Ergebnisse Wir berichten über eine Familie mit einer neuen Mutation in dem selben Gen, einer 9 bp Deletion (c.1418_1425+1del), die jedoch zum gleichen Exonskipping führt. Die klinischen Phenotypen stimmen z. T. mit den berichteten überein.

Schlussfolgerungen Wir fanden eine neue Mutation in PIK3R1 und zeigen, wie breit der resultierende klinische Phänotyp ist.

Key words

PIK3R1 - PI3 kinase delta syndrome - short stature - lymphoproliferation

Schlüsselwörter

PIK3R1 - PI3 Kinase Delta Syndrom - Kleinwuchs - Lymphoproliferation

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