title: Identification of 23 TGFBR2 and 6 TGFBR1 gene mutations and genotype-phenotype investigations in 457 patients with Marfan syndrome type I and II, Loeys-Dietz syndrome and related disorders.
abstract: TGFBR1 and TGFBR2 gene mutations have been associated with Marfan syndrome types 1 and 2, Loeys-Dietz syndrome and isolated familial thoracic aortic aneurysms or dissection. In order to investigate the molecular and clinical spectrum of TGFBR2 mutations we screened the gene in 457 probands suspected of being affected with Marfan syndrome or related disorders that had been referred to our laboratory for molecular diagnosis. We identified and report 23 mutations and 20 polymorphisms. Subsequently, we screened the TGFBR1 gene in the first 74 patients for whom no defect had been found, and identified 6 novel mutations and 12 polymorphisms. Mutation-carrying probands displayed at referral a large clinical spectrum ranging from the Loeys-Dietz syndrome and neonatal Marfan syndrome to isolated aortic aneurysm. Furthermore, a TGFBR1 gene mutation was found in a Shprintzen-Goldberg syndrome patient. Finally, we observed that the yield of mutation detection within the two genes was very low : 4.8% for classical MFS, 4.6% for incomplete MFS and 1% for TAAD in the TGFBR2 gene; 6.2%, 6.2% and 7% respectively in the TGFBR1 gene; in contrast to LDS, where the yield was exceptionally high (87.5%).
authors.affiliation: AP-HP, Hôpital Ambroise Paré, Service de Pédiatrie, Boulogne, F-92100 France. chantal.stheneur@apr.aphp.fr
authors.forename: Chantal
authors.initials: C
authors.lastname: Stheneur
authors.forename: Gwenaëlle
authors.initials: G
authors.lastname: Collod-Béroud
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Laurent
authors.initials: L
authors.lastname: Gouya
authors.forename: Gilles
authors.initials: G
authors.lastname: Sultan
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Le Parc
authors.forename: Bertrand
authors.initials: B
authors.lastname: Moura
authors.forename: David
authors.initials: D
authors.lastname: Attias
authors.forename: Christine
authors.initials: C
authors.lastname: Muti
authors.forename: Marc
authors.initials: M
authors.lastname: Sznajder
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
authors.forename: Claudine
authors.initials: C
authors.lastname: Junien
authors.forename: Clarisse
authors.initials: C
authors.lastname: Baumann
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Marlène
authors.initials: M
authors.lastname: Rio
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Henri
authors.initials: H
authors.lastname: Plauchu
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Bertrand
authors.initials: B
authors.lastname: Chevallier
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jondeau
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D013577:Syndrome
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625841:TGFBR1 protein, human