title: CDKN1C mutations in HELLP/preeclamptic mothers of Beckwith-Wiedemann Syndrome (BWS) patients.
abstract: Preeclampsia is the development of new-onset hypertension with proteinuria after 20 weeks of gestation. HELLP syndrome (haemolysis, elevated liver enzymes, and low platelet count) is a severe form of preeclampsia with high rates of neonatal and maternal morbidity. In recent years, loss of function of cdkn1c (a tight-binding inhibitor of G1 cyclin/cyclin-dependent kinase complexes and a negative regulator of cell proliferation) has been observed in several mouse models of preeclampsia. In this paper, we report on three women with HELLP/preeclampsia who had children with Beckwith Wiedemann syndrome, a complex genetic disorder characterised, among other findings, by overgrowth, omphalocele and macroglossia. All three children displayed mutations in CDKN1C predicted to generate truncated proteins. Two of the mutations were maternally inherited while the third was de novo. This finding suggests a fetal contribution to the maternal disease. To the best of our knowledge this is the first report of CDKN1C mutations in children born to women with preeclampsia/HELLP syndrome, thus suggesting the involvement of an imprinted gene in the pathophysiology of preeclampsia.
authors.affiliation: INGEMM, Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Romanelli
authors.forename: A
authors.initials: A
authors.lastname: Belinchón
authors.forename: A
authors.initials: A
authors.lastname: Campos-Barros
authors.forename: K E
authors.initials: KE
authors.lastname: Heath
authors.forename: S
authors.initials: S
authors.lastname: García-Miñaur
authors.forename: V
authors.initials: V
authors.lastname: Martínez-Glez
authors.forename: R
authors.initials: R
authors.lastname: Palomo
authors.forename: G
authors.initials: G
authors.lastname: Mercado
authors.forename: R
authors.initials: R
authors.lastname: Gracia
authors.forename: P
authors.initials: P
authors.lastname: Lapunzina
mesh_terms: D001483:Base Sequence; D001506:Beckwith-Wiedemann Syndrome / Q000150:complications / Q000235:genetics*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D017359:HELLP Syndrome / Q000209:etiology / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation / Q000502:physiology; D011225:Pre-Eclampsia / Q000209:etiology / Q000235:genetics*; D011247:Pregnancy
chemical_list: C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57