Abstract
The diagnosis of VACTERL syndrome can be elusive, especially in the prenatal life, due to the presence of malformations that overlap those present in other genetic conditions, including the Fanconi anemia (FA). We report on three VACTERL cases within two families, where the two who arrived to be born died shortly after birth due to severe organs' malformations. The suspicion of VACTERL association was based on prenatal ultrasound assessment and postnatal features. Subsequent chromosome breakage analysis suggested the diagnosis of FA. Finally, by next-generation sequencing based on the analysis of the exome in one family and of a panel of Fanconi genes in the second one, we identified novel FANCL truncating mutations in both families. We used ectopic expression of wild-type FANCL to functionally correct the cellular FA phenotype for both mutations. Our study emphasizes that the diagnosis of FA should be considered when VACTERL association is suspected. Furthermore, we show that loss-of-function mutations in FANCL result in a severe clinical phenotype characterized by early postnatal death.
References
May 1, 2001·Nature Biotechnology·E N Noensie, H C Dietz
Sep 16, 2003·Nature Genetics·Amom Ruhikanta MeeteiWeidong Wang
Nov 25, 2003·Blood·Marieke LevitusHans Joenje
Jul 15, 2005·American Journal of Medical Genetics. Part a·Laurence FaivreClarisse Baumann
Apr 14, 2006·British Journal of Haematology·Kirsten HuckDetlev Schindler
Apr 23, 2008·Current Protocols in Human Genetics·Arleen D Auerbach
May 1, 2009·Human Mutation·Abdullah Mahmood AliAmom Ruhikanta Meetei
May 9, 2009·Blood·Thiyam Ramsing SinghAmom Ruhikanta Meetei
May 26, 2009·Mutation Research·Kornelia NevelingDetlev Schindler
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Jul 21, 2010·Genome Research·Aaron McKennaMark A DePristo
Jan 29, 2011·Blood·Maria CastellaJordi Surrallés
Jul 20, 2011·Molecular Genetics and Metabolism·Benjamin D SolomonJames C Mullikin
Aug 19, 2011·Orphanet Journal of Rare Diseases·Benjamin D Solomon
Oct 8, 2011·Genes & Development·Anna Klingseisen, Andrew P Jackson
Apr 21, 2012·Briefings in Bioinformatics·Helga ThorvaldsdóttirJill P Mesirov
Jun 14, 2012·Anemia·Anneke B OostraJohan P de Winter
Jun 22, 2012·Anemia·Najim AmezianeJohan P de Winter
Dec 27, 2012·Disease Models & Mechanisms·Sietske T BakkerHein te Riele
Mar 13, 2013·Blood·Immacolata AndolfoAchille Iolascon
Apr 25, 2013·Blood·Settara C ChandrasekharappaUNKNOWN NISC Comparative Sequencing Program
May 3, 2013·Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine·Jada G HamiltonPaul K J Han
Mar 14, 2014·Nucleic Acids Research·Simonne LongerichPatrick Sung
Jun 26, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kishan A T NaipalDik C van Gent
Citations
Nov 23, 2015·American Journal of Medical Genetics. Part a·Sharon A SavageUNKNOWN NCI DCEG Cancer Sequencing Working Group
Mar 31, 2016·American Journal of Medical Genetics. Part a·Blanche P Alter, Neelam Giri
Jun 19, 2015·Human Molecular Genetics·Elizabeth L VirtsHelmut Hanenberg
Dec 18, 2016·Indian Journal of Pediatrics·Rosalba Sevilla-MontoyaPatricia Grether
Feb 16, 2017·European Journal of Human Genetics : EJHG·Annalisa VetroOrsetta Zuffardi
Aug 13, 2017·Pediatric Blood & Cancer·Neelam GiriBlanche P Alter
Sep 13, 2019·Human Mutation·Frank X DonovanBabu Rao Vundinti
Aug 17, 2019·Journal of Developmental Biology·Philippa Harding, Mariya Moosajee
Oct 25, 2020·American Journal of Medical Genetics. Part a·David A DymentA Micheil Innes
Dec 5, 2020·Human Molecular Genetics·Ella M M A MartinGavin Chapman
Mar 18, 2021·European Journal of Human Genetics : EJHG·Beatrice SpedicatiGiorgia Girotto
Sep 30, 2021·Human Mutation·Merin GeorgeBabu Rao Vundinti