title: Could a patient with SMC1A duplication be classified as a human cohesinopathy?
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.
authors.affiliation: Unit of Clinical Genetics and Functional Genomics, Departments of Pharmacology-Physiology and Pediatrics, Medical School, University of Zaragoza, Zaragoza, Spain; Service of Pediatrics, Hospital Clínico Universitario "Lozano Blesa", Zaragoza, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Baquero-Montoya
authors.forename: M C
authors.initials: MC
authors.lastname: Gil-Rodríguez
authors.forename: M E
authors.initials: ME
authors.lastname: Teresa-Rodrigo
authors.forename: M
authors.initials: M
authors.lastname: Hernández-Marcos
authors.forename: G
authors.initials: G
authors.lastname: Bueno-Lozano
authors.forename: I
authors.initials: I
authors.lastname: Bueno-Martínez
authors.forename: S
authors.initials: S
authors.lastname: Remeseiro
authors.forename: R
authors.initials: R
authors.lastname: Fernández-Hernández
authors.forename: M
authors.initials: M
authors.lastname: Bassecourt-Serra
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez de Alba
authors.forename: E
authors.initials: E
authors.lastname: Queralt
authors.forename: A
authors.initials: A
authors.lastname: Losada
authors.forename: B
authors.initials: B
authors.lastname: Puisac
authors.forename: F J
authors.initials: FJ
authors.lastname: Ramos
authors.forename: J
authors.initials: J
authors.lastname: Pié
mesh_terms: D000293:Adolescent; D018797:Cell Cycle Proteins / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D041321:Chromosomes, Human, X; D003635:De Lange Syndrome / Q000235:genetics* / Q000503:physiopathology; D020131:Genes, Duplicate; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D010641:Phenotype; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1
keywords: CdLS; Cornelia de Lange Syndrome; SMC1A duplication; human cohesinopathy; sSMC; small Supernumerary Marker Chromosome