Clinical and molecular data in cases of prenatal localized overgrowth disorder: major implication of genetic variants in PI3K-AKT-mTOR signaling pathway.
PI3K-AKT-mTOR
cultured amniocytes
genetic counseling
localized overgrowth disorder
postzygotic
prenatal diagnosis
Journal
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology
ISSN: 1469-0705
Titre abrégé: Ultrasound Obstet Gynecol
Pays: England
ID NLM: 9108340
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
13
06
2021
received:
19
02
2021
accepted:
14
06
2021
pubmed:
26
6
2021
medline:
6
4
2022
entrez:
25
6
2021
Statut:
ppublish
Résumé
To describe clinical and molecular findings in a French multicenter cohort of fetuses with prenatal diagnosis of congenital abnormality and suspicion of a localized overgrowth disorder (LOD) suggestive of genetic variants in the PI3K-AKT-mTOR signaling pathway. We analyzed retrospectively data obtained between 1 January 2013 and 1 May 2020 from fetuses with brain and/or limb overgrowth referred for molecular diagnosis of PI3K-AKT-mTOR pathway genes by next-generation sequencing (NGS) using pathological tissue obtained by fetal autopsy. We also assessed the diagnostic yield of amniotic fluid. During the study period, 21 subjects with LOD suspected of being secondary to a genetic variant of the PI3K-AKT-mTOR pathway were referred for analysis. Of these, 17 fetuses had brain overgrowth, including six with isolated megalencephaly (MEG) and 11 with hemimegalencephaly (HMEG). Of the six with MEG, germline variants were identified in four cases, in either PIK3R2, AKT3 or MTOR, and a postzygotic PIK3R2 variant was found in the other two cases. Of the 11 with HMEG, a postzygotic PIK3CA variant was found in three fetuses with extracerebral features of PIK3CA-related overgrowth spectrum, and in seven fetuses with isolated HMEG. No pathogenic variant was identified in the 11 Isolated MEG or HMEG may lead to identification of genetic variants in the PI3K-AKT-mTOR signaling pathway. Cases of limb overgrowth and LM or isolated HMEG are likely associated with PIK3CA variants. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Substances chimiques
MTOR protein, human
EC 2.7.1.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
532-542Investigateurs
Emilie Tisserand
(E)
Martin Chevarin
(M)
Julian Delanne
(J)
Thibaud Jouan
(T)
Charlotte Pöe
(C)
Carine Abel
(C)
Patrick Allory
(P)
Daniel Amram
(D)
Tania Attie-Bitach
(T)
Jacqueline Aziza
(J)
Jean-Baptiste Benevent
(JB)
Laurent Bidat
(L)
Bettina Bessières
(B)
Françoise Boussion
(F)
Anne-Sophie Cabaret-Dufour
(AS)
Geneviève Chanoz-Poulard
(G)
Nicolas Chassaing
(N)
Viorica Ciorna-Monferrato
(V)
Anne-Gaëlle Cordier
(AG)
Marie-Pierre Cordier
(MP)
Fabrice Cuillier
(F)
Berenice Doray
(B)
Ferechte Encha-Razavi
(F)
Marie-Laure Eszto
(ML)
Catherine Fallet Bianco
(CF)
Carla Fernandez
(C)
Mathilde Ferry
(M)
Axel Fichez
(A)
Valérie Goua Vequeau
(VG)
David Grevent
(D)
Agnès Guichet
(A)
Nicole Laurent
(N)
Marie-Pascale Le Gac
(MP)
Mathilde Lefebvre
(M)
Pascaline Letard
(P)
Philippe Loget
(P)
Didier Loisel
(D)
Jelena Martinovich
(J)
Jean-Paul Masutti
(JP)
Anne-Elodie Millischer
(AE)
Yuri Musizzano
(Y)
Jean-François Nord
(JF)
Marie-Josée Perez
(MJ)
Fabienne Prieur
(F)
Maia Proisy
(M)
Chloé Quelin
(C)
Philippe Roth
(P)
Thierry Rousseau
(T)
Laurent Salomon
(L)
Pascale Sonigo
(P)
Emmanuel Spaggiari
(E)
Noëlle Stempfle
(N)
Julien Stirnemann
(J)
Julia Tanteau
(J)
Stéphane Triau
(S)
Alexandre Vasiljevic
(A)
Yves Ville
(Y)
Merzouka Zidane-Marinnes
(M)
Sophie Kaltenbach
(S)
Jean-Baptiste Rivière
(JB)
Informations de copyright
© 2021 International Society of Ultrasound in Obstetrics and Gynecology.
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