Insertion of Alu elements at a PTEN hotspot in Cowden syndrome

European Journal of Human Genetics : EJHG
Louise CrivelliM Longy

Abstract

Cowden syndrome (CS) is an inherited autosomal dominant disorder associated with germline pathogenic variants of the PTEN tumor suppressor gene. Its phenotypical expression is highly variable and the existence of patients with a CS suggestive phenotype without pathogenic PTEN variant may be related to genetic heterogeneity. In order to explore this hypothesis through the detection of potentially deleterious variants enabling us to identify a new candidate gene, we performed whole-exome sequencing (WES) in a series of 22 CS patients without detectable PTEN pathogenic variant using conventional methods for mutation screening. We failed to identify a novel candidate gene, but interestingly in two patients WES revealed the presence of two distinct, previously undescribed Alu insertions with the same break points in exon 5. These insertions were not found in a series of 35 breast carcinomas that showed a loss of PTEN expression without a detectable alteration of this gene. This study reveals the presence of a PTEN Alu insertion hotspot involved in CS, and suggests that undetected PTEN pathogenic variants could contribute to CS.

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Citations

Jul 12, 2018·Journal of Clinical Immunology·Jérémie RosainJacinta Bustamante
Oct 2, 2019·Cold Spring Harbor Perspectives in Medicine·Joanne Ngeow, Charis Eng
Aug 23, 2019·Annual Review of Medicine·Lamis YehiaCharis Eng
Jan 8, 2019·The Journal of Clinical Investigation·Lamis YehiaCharis Eng
May 24, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Julie LeclercMarie-Pierre Buisine
Nov 11, 2020·Clinical Genetics·Clarisse DelvalléeJean Muller

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