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2009 | 50 | 4 |

Tytuł artykułu

A new sporadic case of early-onset Loeys-Dietz syndrome due to the recurrent mutation p.R528C in the TGFBR2 gene substantiates interindividual clinical variability

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
We report on a 2-year-old Polish girl with typical manifestations of Loeys-Dietz syndrome (LDS), a rare genetic condition belonging to the group of Marfan-related disorders. The characteristic LDS symptoms observed in the girl included craniofacial dysmorphism (craniosynostosis, cleft palate, hypertelorism), arachnodactyly, camptodactyly, scoliosis, joint laxity, talipes equinovarus, translucent and hyperelastic skin, and umbilical hernia. Mild dilatation of the ascending aorta and tortuous course of the left internal carotid artery were recognized during her second year of life. Molecular genetic testing revealed a heterozygous missense mutation (c.1582C>T, p.R528C) in the transforming growth factor beta receptor II gene (TGFBR2). This mutation has been previously associated with LDS in 5 unrelated cases, and was never reported in patients with other Marfan-related disorders. Comparison of the phenotypes of our patient and these 5 individuals with c.1582C>T showed that only the hallmark triad of the syndrome - consisting of hypertelorism, aortic root dilatation/aneurysm, and cleft palate or bifid uvula - was present in all 6 cases. Interestingly, none of the 5 individuals who underwent psychological evaluation showed developmental delay. The pattern of all other LDS features showed interindividual variability. Our data support the recently reported observation that symptoms of LDS can develop at a very young age, making early diagnosis and management essential for these patients. This is the first report on a Polish infant with typical LDS symptoms caused by a TGFBR2 mutation.

Wydawca

-

Rocznik

Tom

50

Numer

4

Opis fizyczny

p.405-410,fig.,ref.

Twórcy

autor
  • Department of Medical Genetics, University of Medical Sciences in Poznan, Grunwaldzka 55, paw.15, 60-352 Poznan, Poland
  • Center for Medical Genetics in Poznań, Poland
autor
  • University of Zurich, Institute of Medical Genetics, Division of Medical Molecular Genetics and Gene Diagnostics, Zurich, Switzerland
autor
  • Department of General Nursery and Department of Pediatrics, Hematology, Oncology and Endocrinology, Medical University of Gdańsk, Poland
autor
  • Center for Medical Genetics, Ghent University Hospital, ghent, Belgium
autor
  • Center for Medical Genetics, Ghent University Hospital, ghent, Belgium
autor
  • AP-HP, Hopital Ambroise Pare, Service de Pediatrie, Boulogne, France
  • AP-HP, Hopital Bichat, Consultation multidisciplinaire Marfan, Paris, France
autor
  • Department of Medical Genetics, University of Medical Sciences in Poznan, Grunwaldzka 55, paw.15, 60-352 Poznan, Poland
  • Department of Medical Genetics, University of Medical Sciences in Poznan, Grunwaldzka 55, paw.15, 60-352 Poznan, Poland
autor
  • University of Zurich, Institute of Medical Genetics, Division of Medical Molecular Genetics and Gene Diagnostics, Zurich, Switzerland
  • Department of Medical Genetics, University of Medical Sciences in Poznan, Grunwaldzka 55, paw.15, 60-352 Poznan, Poland
  • Center for Medical Genetics in Poznań, Poland

Bibliografia

  • Aalberts JJ, van den Berg MP, Bergman JE, du Marchie Sarvaas GJ, Post JG, van Unen H, et al. 2008. The many faces of aggressive aortic pathology: Loeys-Dietz syndrome. Neth Heart J 16: 299-304.
  • Ades LC, Sullivan K, Biggin A, Haan EA, Brett M, Holman KJ, et al. 2006. FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited. Am J Med Genet A 140: 1047-1058.
  • Akutsu K, Morisaki H, Takeshita S, Sakamoto S, Tamori Y, Yoshimuta T, et al. 2007. Phenotypic heterogeneity of Marfan-like connective tissue disorders associated with mutations in the transform ing growth factor-beta receptor genes. Circ J 71: 1305-1309.
  • Disabella E, Grasso M, Marziliano N, Ansaldi S, Lucchelli C, Porcu E, et al. 2006. Two novel and one known mutation of the TGFBR2 gene in Marfan syndrome not associated with FBN1 gene defects. Eur J Hum Genet 14: 34-38.
  • Frederic MY, Hamroun D, Faivre L, Boileau C, Jondeau G, Claustres M, et al. 2008. A new locus-specific database (LSDB) for mutations in the TGFBR2 gene: UMD-TGFBR2. Hum Mutat 29: 33-38.
  • LeMaire SA, Pannu H, Tran-Fadulu V, Carter SA, Coselli JS, Milewicz DM, 2007. Severe aortic and arterial aneurysms associated with a TGFBR2 mutation. Nat Clin Pract Cardiovasc Med 4: 167-171.
  • Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, et al. 2005. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet 37: 275-281.
  • Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, et al. 2006. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med 355: 788-798.
  • Matyas G, Arnold E, Carrel T, Baumgartner D, Boileau C, Berger W, Steinmann B, 2006. Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome-related disorders. Hum Mutat 27: 760-769.
  • Matyas G, Alonso S, Patrignani A, Marti M, Arnold E, Magyar I, et al. 2007. Large genomic fibrillin-1 (FBN1) gene deletions provide evidence for true haploinsufficiency in Marfan syndrome. Hum Genet 122: 23-32.
  • Mizuguchi T, Collod-Beroud G, Akiyama T, Abifadel M, Harada N, Morisaki T, et al. 2004. Heterozygous TGFBR2 mutations in Marfan syndrome. Nat Genet 36: 855-860.
  • Sakai H, Visser R, Ikegawa S, Ito E, Numabe H, Watanabe Y, et al. 2006. Comprehensive genetic analysis of relevant four genes in 49 patients with Marfan syndrome or Marfan-related phenotypes. Am J Med Genet A 140: 1719-17125.
  • Singh KK, Rommel K, Mishra A, Karck M, Haverich A, Schmidtke J, Arslan-Kirchner M, 2006. TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys-Dietz syndrome. Hum Mutat 27: 770-777.
  • Stheneur C, Collod-Beroud G, Faivre L, Gouya L, Sultan G, Le Pare JM, et al. 2008. 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. Hum Mutat 29: E284-295.
  • Togashi Y, Sakoda H, Nishimura A, Matsumoto N, Hiraoka H, Matsuzawa Y, 2007. A Japanese family of typical Loeys-Dietz syndrome with a TGFBR2 mutation. Intern Med 46: 1995-2000.
  • Yetman AT, Beroukhim RS, Ivy DD, Manchester D, Importance of the clinical recognition of Loeys-Dietz syndrome in the neonatal period. Pediatrics 119: el 199-202.

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Bibliografia

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