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

Authors

  • Juan Pié,

    Corresponding author
    1. Laboratory of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, 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.
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  • María Concepción Gil-Rodríguez,

    1. Laboratory of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
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  • Milagros Ciero,

    1. Laboratory of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
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  • Eduardo López-Viñas,

    1. Molecular Modelling Group, Center of Molecular Biology “Severo Ochoa” (CSIC-UAM), Cantoblanco, Madrid, Spain
    2. “CIBER-Obn Physiopathology of Obesity and Nutrition” (CB06/03/0026), Instituto de Salud Carlos III, Madrid, Spain
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  • María Pilar Ribate,

    1. Laboratory of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
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  • María Arnedo,

    1. Laboratory of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
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  • Matthew A. Deardorff,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Beatriz Puisac,

    1. Laboratory of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
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  • Jesús Legarreta,

    1. Laboratory of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
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  • Juan Carlos de Karam,

    1. Laboratory of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
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  • Encarnación Rubio,

    1. Unit of Biostatistic, Department of Microbiology, Preventive Medicine and Public Health, Medical School, University of Zaragoza, Zaragoza, Spain
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  • Inés Bueno,

    1. Laboratory of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
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  • Antonio Baldellou,

    1. Service of Pediatrics and Molecular Genetics Laboratory, Hospital Universitario Miguel Servet, Zaragoza, Spain
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  • Mª Teresa Calvo,

    1. Service of Pediatrics and Molecular Genetics Laboratory, Hospital Universitario Miguel Servet, Zaragoza, Spain
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  • Nuria Casals,

    1. “CIBER-Obn Physiopathology of Obesity and Nutrition” (CB06/03/0026), Instituto de Salud Carlos III, Madrid, Spain
    2. Department of Biochemistry and Molecular Biology, School of Health Sciences, International University of Catalonia, Sant Cugat, Barcelona, Spain
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  • José Luis Olivares,

    1. Laboratory of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
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  • Ana Losada,

    1. Spanish National Cancer Research Center, Madrid, Spain
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  • Fausto G. Hegardt,

    1. “CIBER-Obn Physiopathology of Obesity and Nutrition” (CB06/03/0026), Instituto de Salud Carlos III, Madrid, Spain
    2. Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Barcelona, Spain
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  • Ian D. Krantz,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Paulino Gómez-Puertas,

    1. Molecular Modelling Group, Center of Molecular Biology “Severo Ochoa” (CSIC-UAM), Cantoblanco, Madrid, Spain
    2. “CIBER-Obn Physiopathology of Obesity and Nutrition” (CB06/03/0026), Instituto de Salud Carlos III, Madrid, Spain
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  • Feliciano J. Ramos

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

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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