Research Article

Mutations and variants in the cohesion factor genes NIPBL, SMC1A, and SMC3 in a cohort of 30 unrelated patients with Cornelia de Lange syndrome†

  1. Juan Pié1,*,
  2. María Concepción Gil-Rodríguez1,
  3. Milagros Ciero1,
  4. Eduardo López-Viñas2,3,
  5. María Pilar Ribate1,
  6. María Arnedo1,
  7. Matthew A. Deardorff4,
  8. Beatriz Puisac1,
  9. Jesús Legarreta1,
  10. Juan Carlos de Karam1,
  11. Encarnación Rubio5,
  12. Inés Bueno1,
  13. Antonio Baldellou6,
  14. Mª Teresa Calvo6,
  15. Nuria Casals3,7,
  16. José Luis Olivares1,
  17. Ana Losada8,
  18. Fausto G. Hegardt3,9,
  19. Ian D. Krantz4,
  20. Paulino Gómez-Puertas2,3,
  21. Feliciano J. Ramos1

Article first published online: 26 MAR 2010

DOI: 10.1002/ajmg.a.33348

Issue

American Journal of Medical Genetics Part A

American Journal of Medical Genetics Part A

Volume 152A, Issue 4, pages 924–929, April 2010

Additional Information

How to Cite

Pié, J., Gil-Rodríguez, M. C., Ciero, M., López-Viñas, E., Ribate, M. P., Arnedo, M., Deardorff, M. A., Puisac, B., Legarreta, J., de Karam, J. C., Rubio, E., Bueno, I., Baldellou, A., Calvo, M. T., Casals, N., Olivares, J. L., Losada, A., Hegardt, F. G., Krantz, I. D., Gómez-Puertas, P. and Ramos, F. J. (2010), Mutations and variants in the cohesion factor genes NIPBL, SMC1A, and SMC3 in a cohort of 30 unrelated patients with Cornelia de Lange syndrome. Am. J. Med. Genet., 152A: 924–929. doi: 10.1002/ajmg.a.33348

Author Information

  1. 1

    Laboratory of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain

  2. 2

    Molecular Modelling Group, Center of Molecular Biology “Severo Ochoa” (CSIC-UAM), Cantoblanco, Madrid, Spain

  3. 3

    “CIBER-Obn Physiopathology of Obesity and Nutrition” (CB06/03/0026), Instituto de Salud Carlos III, Madrid, Spain

  4. 4

    Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

  5. 5

    Unit of Biostatistic, Department of Microbiology, Preventive Medicine and Public Health, Medical School, University of Zaragoza, Zaragoza, Spain

  6. 6

    Service of Pediatrics and Molecular Genetics Laboratory, Hospital Universitario Miguel Servet, Zaragoza, Spain

  7. 7

    Department of Biochemistry and Molecular Biology, School of Health Sciences, International University of Catalonia, Sant Cugat, Barcelona, Spain

  8. 8

    Spanish National Cancer Research Center, Madrid, Spain

  9. 9

    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Barcelona, Spain

*Laboratory of Clinical Genetics and Functional Genomics, Department of Pharmacology and Physiology, University of Zaragoza Medical School, c/Domingo Miral s/n, Zaragoza E-50009, Spain.

  1. †

    How to cite this article: Pié J, Gil-Rodríguez MC, Ciero M, López-Viñas E, Ribate MP, Arnedo M, Deardorff MA, Puisac B, Legarreta J, de Karam JC, Rubio E, Bueno I, Baldellou A, Calvo MªT, Casals N, Olivares JL, Losada A, Hegardt FG, Krantz ID, Gómez-Puertas P, Ramos FJ. 2010. Mutations and variants in the cohesion factor genes NIPBL, SMC1A, and SMC3 in a cohort of 30 unrelated patients with Cornelia de Lange syndrome. Am J Med Genet Part A 152A:924–929.

Publication History

  1. Issue published online: 26 MAR 2010
  2. Article first published online: 26 MAR 2010
  3. Manuscript Accepted: 11 DEC 2009
  4. Manuscript Received: 1 AUG 2008

Funded by

  • Spanish Ministry of Health-Fondo de Investigación Sanitaria (FIS). Grant Number: PI061343
  • Diputación General de Aragón (DGA, Grupo Consolidado B20)
  • Spanish Ministry of Education and Science. Grant Number: SAF2004-06843
  • Comunidad de Madrid´s Activities Program R&D Groups in Biosciences. Grant Number: S-BIO-0260/2006-COMBACT
  • Ajut de Suport als Grups de Recerca de Catalunya. Grant Number: 2005SGR-00733
  • NICHD. Grant Number: 5PO1HD052860
  • Fundación Ramón Areces
  • Banco Santander Central Hispano. Grant Number: B120/2006
  • Diputación General de Aragón. Grant Number: B120/2006

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Keywords:

  • Cornelia de Lange syndrome (CdLS);
  • NIPBL;
  • SMC1A;
  • SMC3;
  • genes;
  • mutations

Abstract

Cornelia de Lange syndrome (CdLS) manifests facial dysmorphic features, growth and cognitive impairment, and limb malformations. Mutations in three genes (NIPBL, SMC1A, and SMC3) of the cohesin complex and its regulators have been found in affected patients. Here, we present clinical and molecular characterization of 30 unrelated patients with CdLS. Eleven patients had mutations in NIPBL (37%) and three patients had mutations in SMC1A (10%), giving an overall rate of mutations of 47%. Several patients shared the same mutation in NIPBL (p.R827GfsX2) but had variable phenotypes, indicating the influence of modifiers in CdLS. Patients with NIPBL mutations had a more severe phenotype than those with mutations in SMC1A or those without identified mutations. However, a high incidence of palate defects was noted in patients with SMC1A mutations. In addition, we observed a similar phenotype in both male and female patients with SMC1A mutations. Finally, we report the first patient with an SMC1A mutation and the Sandifer complex. © 2010 Wiley-Liss, Inc.

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