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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2019

Open Access 01-12-2019 | Ehlers-Danlos Syndrome | Research

Outcomes of 4 years of molecular genetic diagnosis on a panel of genes involved in premature aging syndromes, including laminopathies and related disorders

Authors: Maude Grelet, Véronique Blanck, Sabine Sigaudy, Nicole Philip, Fabienne Giuliano, Khaoula Khachnaoui, Godelieve Morel, Sarah Grotto, Julia Sophie, Céline Poirsier, James Lespinasse, Laurent Alric, Patrick Calvas, Gihane Chalhoub, Valérie Layet, Arnaud Molin, Cindy Colson, Luisa Marsili, Patrick Edery, Nicolas Lévy, Annachiara De Sandre-Giovannoli

Published in: Orphanet Journal of Rare Diseases | Issue 1/2019

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Abstract

Background

Segmental progeroid syndromes are a heterogeneous group of rare and often severe genetic disorders that have been studied since the twentieth century. These progeroid syndromes are defined as segmental because only some of the features observed during natural aging are accelerated.

Methods

Since 2015, the Molecular Genetics Laboratory in Marseille La Timone Hospital proposes molecular diagnosis of premature aging syndromes including laminopathies and related disorders upon NGS sequencing of a panel of 82 genes involved in these syndromes.
We analyzed the results obtained in 4 years on 66 patients issued from France and abroad.

Results

Globally, pathogenic or likely pathogenic variants (ACMG class 5 or 4) were identified in about 1/4 of the cases; among these, 9 pathogenic variants were novel. On the other hand, the diagnostic yield of our panel was over 60% when the patients were addressed upon a nosologically specific clinical suspicion, excepted for connective tissue disorders, for which clinical diagnosis may be more challenging. Prenatal testing was proposed to 3 families. We additionally detected 16 variants of uncertain significance and reclassified 3 of them as benign upon segregation analysis in first degree relatives.

Conclusions

High throughput sequencing using the Laminopathies/ Premature Aging disorders panel allowed molecular diagnosis of rare disorders associated with premature aging features and genetic counseling for families, representing an interesting first-level analysis before whole genome sequencing may be proposed, as a future second step, by the National high throughput sequencing platforms (“Medicine France Genomics 2025” Plan), in families without molecular diagnosis.
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Metadata
Title
Outcomes of 4 years of molecular genetic diagnosis on a panel of genes involved in premature aging syndromes, including laminopathies and related disorders
Authors
Maude Grelet
Véronique Blanck
Sabine Sigaudy
Nicole Philip
Fabienne Giuliano
Khaoula Khachnaoui
Godelieve Morel
Sarah Grotto
Julia Sophie
Céline Poirsier
James Lespinasse
Laurent Alric
Patrick Calvas
Gihane Chalhoub
Valérie Layet
Arnaud Molin
Cindy Colson
Luisa Marsili
Patrick Edery
Nicolas Lévy
Annachiara De Sandre-Giovannoli
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2019
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-019-1189-z

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