Get access

Could a patient with SMC1A duplication be classified as a human cohesinopathy?

Authors

  • C. Baquero-Montoya,

    1. Unit of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
    2. Service of Pediatrics, Hospital Clínico Universitario “Lozano Blesa”, Zaragoza, Spain
    Search for more papers by this author
  • M.C. Gil-Rodríguez,

    1. Unit of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
    Search for more papers by this author
  • M.E. Teresa-Rodrigo,

    1. Unit of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
    Search for more papers by this author
  • M. Hernández-Marcos,

    1. Unit of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
    Search for more papers by this author
  • G. Bueno-Lozano,

    1. Service of Pediatrics, Hospital Clínico Universitario “Lozano Blesa”, Zaragoza, Spain
    Search for more papers by this author
  • I. Bueno-Martínez,

    1. Unit of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
    2. Service of Pediatrics, Hospital Clínico Universitario “Lozano Blesa”, Zaragoza, Spain
    Search for more papers by this author
  • S. Remeseiro,

    1. Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
    Search for more papers by this author
  • R. Fernández-Hernández,

    1. Cell Cycle Group, Cancer Epigenetics and Biology Program (PEBC), Institut d'Investigacions Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
    Search for more papers by this author
  • M. Bassecourt-Serra,

    1. Department of Molecular Genetics, Hospital Universitario “Miguel Servet”, Zaragoza, Spain
    Search for more papers by this author
  • M. Rodríguez de Alba,

    1. Department of Genetics, Fundación Jiménez Díaz, Madrid, Spain
    Search for more papers by this author
  • E. Queralt,

    1. Cell Cycle Group, Cancer Epigenetics and Biology Program (PEBC), Institut d'Investigacions Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
    Search for more papers by this author
  • A. Losada,

    1. Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain
    Search for more papers by this author
  • B. Puisac,

    1. Unit of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
    Search for more papers by this author
  • F.J. Ramos,

    1. Unit of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
    2. Service of Pediatrics, Hospital Clínico Universitario “Lozano Blesa”, Zaragoza, Spain
    Search for more papers by this author
  • J. Pié

    Corresponding author
    1. Unit of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain
    • Corresponding author: Juan Pié, MD, PhD, Unit of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology, University of Zaragoza, Medical School, c/ Domingo Miral s/n, Zaragoza E-50009, Spain

      Tel.: +34 976 76 16 77;

      fax: +34 976 76 17 00;

      e-mail: juanpie@unizar.es

    Search for more papers by this author

  • All authors declare no conflict of interest.

Abstract

The disorders caused by mutations in genes encoding subunits and accessory proteins of cohesin complex are collectively termed as cohesinopathies. The best known cohesinopathy is Cornelia de Lange Syndrome (CdLS), which is a multisystem developmental disorder characterized by facial dysmorphism, limb malformations, growth and cognitive impairment. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), are responsible for ∼70% of CdLS cases. We describe a 16-year-old boy with facial dysmorphism, growth retardation, intellectual disability, hirsutism and small hands, who has a small Supernumerary Marker Chromosome (sSMC) present in mosaic form. sSMC is composed of two duplicated segments encompassing 17 genes including SMC1A gene, at the regions Xp11.22 and Xp11.21q11.1. Clinical comparison between our patient with a previously reported individual with a SMC1A duplication and four male carriers of similar sSMC reported in databases, suggest that they all share clinical features related to cohesinopathies. Although our patient does not have the classical CdLS craniofacial phenotype, he has pre and postnatal growth retardation, intellectual disability and mild musculoskeletal anomalies, features commonly seen in patients with cohesinopathies.

Ancillary