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ELN gene triplication responsible for familial supravalvular aortic aneurysm

Published online by Cambridge University Press:  17 June 2014

Anne-Sophie Guemann ,
Joris Andrieux ,
Florence Petit ,
Emmanuel Halimi ,
Sonia Bouquillon ,
Sylvie Manouvrier-Hanu ,
Jiddeke Van De Kamp ,
Catherine Boileau ,
Nadine Hanna  and
Guillaume Jondeau
...Show all authors
Anne-Sophie Guemann
Affiliation:
Department of Clinical Genetics, Lille, Jeanne de Flandre Hospital, CHRU Lille, France
Joris Andrieux
Affiliation:
Department of Cytogenetics, Lille, Jeanne de Flandre Hospital, CHRU Lille, France
Florence Petit
Affiliation:
Department of Clinical Genetics, Lille, Jeanne de Flandre Hospital, CHRU Lille, France Lille Nord de France University, France
Emmanuel Halimi
Affiliation:
Department of Clinical Genetics, Lille, Jeanne de Flandre Hospital, CHRU Lille, France
Sonia Bouquillon
Affiliation:
Department of Cytogenetics, Lille, Jeanne de Flandre Hospital, CHRU Lille, France
Sylvie Manouvrier-Hanu
Affiliation:
Department of Clinical Genetics, Lille, Jeanne de Flandre Hospital, CHRU Lille, France Lille Nord de France University, France
Jiddeke Van De Kamp
Affiliation:
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
Catherine Boileau
Affiliation:
Laboratory of Biochemistry and Molecular Genetics, Amboise Paré Hospital, Boulogne, France
Nadine Hanna
Affiliation:
InsermU745, Faculty of Pharmaceutical and Biological Sciences, University Paris Descartes, Paris, France
Guillaume Jondeau
Affiliation:
AP-HP, National Reference Centre for Marfan syndrome, Bichat Hospital, Paris, France
Guy Vaksmann
Affiliation:
Department of Cardiology, La Louvière Hospital, Lille, France
Veronique Houfflin-Debarge
Affiliation:
Lille Nord de France University, France Department of Obstetrics, Jeanne de Flandre Hospital, CHRU Lille, France
Muriel Holder-Espinasse*
Affiliation:
Department of Clinical Genetics, Lille, Jeanne de Flandre Hospital, CHRU Lille, France Lille Nord de France University, France Department of Clinical Genetics, Guy’s Hospital, London, United Kingdom
*
Correspondence to: Dr M. Holder, Consultant in Clinical Genetics, 7th Floor Borough Wing, Guy’s Hospital, Great Maze Pond, London SE1 9RT, United Kingdom. Tel: 00442071881362; Fax: 00442071881369; E-mail: muriel.holder@gstt.nhs.uk
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Abstract

Supravalvular aortic aneurysms are less frequent than abdominal ones. Among Supravalvular aortic aneurysm aetiologies, we focused on dystrophic lesions as they can be secondary to genetic causes such as elastin anomaly. We report on a familial 7q11.23 triplication – including the ELN gene – segregating with a supravalvular aortic aneurysm. During her first pregnancy, our index patient was diagnosed with tuberous sclerosis and with a Supravalvular aortic aneurysm. The foetus was affected equally. For the second pregnancy, parents applied for preimplantation diagnosis, and a subsequent prenatal diagnosis was offered to the couple, comprising TSC1 molecular analysis, karyotype, and multiplex ligation probe amplification. TSC1 mutation was not found on foetal deoxyribo nucleic acid. Foetal karyotype was normal, but multiplex ligation probe amplification detected a 7q11.23 duplication. Quantitative-polymerase chain reaction and array-comparative genomic hybridisation carried out to further assess this chromosome imbalance subsequently identified a 7q11.23 triplication involving ELN and LIMK1. Foetal heart ultrasound identified a Supravalvular aortic aneurysm. A familial screening was offered for the 7q11.23 triplication and, when found, heart ultrasound was performed. The triplication was diagnosed in our index case as well as in her first child. Of the 17 individuals from this family, 11 have the triplication. Of the 11 individuals with the triplication, 10 were identified to have a supravalvular aortic aneurysm. Of them, two individuals received a medical treatment and one individual needed surgery. We provide evidence of supravalvular aortic aneurysm segregating with 7q11.23 triplication in this family. We would therefore recommend cardiac surveillance for individuals with 7q11.23 triplication. It would also be interesting to offer a quantitative-polymerase chain reaction or an array-comparative genomic hybridisation to a larger cohort of patients presenting with isolated supravalvular aortic aneurysm, as it may provide further information.

Keywords

7q11.23 triplicationELNsupravalvular aortic aneurysm
Type
Original Articles
Information
Cardiology in the Young , Volume 25 , Issue 4 , April 2015 , pp. 712 - 717
Copyright
© Cambridge University Press 2014 

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