title: Two novel POC1A mutations in the primordial dwarfism, SOFT syndrome: Clinical homogeneity but also unreported malformations.
abstract: Primordial dwarfism encompasses rare conditions characterized by severe intrauterine growth retardation and growth deficiency throughout life. Recently, three POC1A mutations have been reported in six families with the primordial dwarfism, SOFT syndrome (Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis). Using a custom-designed Next-generation sequencing skeletal dysplasia panel, we have identified two novel homozygous POC1A mutations in two individuals with primordial dwarfism. The severe growth retardation and the facial profiles are strikingly similar between our patients and those described previously. However, one of our patients was diagnosed with severe foramen magnum stenosis and subglottic tracheal stenosis, malformations not previously associated with this syndrome. Our findings confirm that POC1A mutations cause SOFT syndrome and that mutations in this gene should be considered in patients with severe pre- and postnatal short stature, symmetric shortening of long bones, triangular facies, sparse hair and short, thickened distal phalanges.
authors.affiliation: Institute of Medical & Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto Carlos III, Madrid, Spain.|Multidisciplinary Skeletal Dysplasia Unit (UMDE), Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Jimena
authors.initials: J
authors.lastname: Barraza-García
authors.affiliation: Institute of Medical & Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.|Multidisciplinary Skeletal Dysplasia Unit (UMDE), Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Iván Rivera-Pedroza
authors.affiliation: Department of Pediatric Endocrinology, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Salamanca
authors.affiliation: Institute of Medical & Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto Carlos III, Madrid, Spain.|Multidisciplinary Skeletal Dysplasia Unit (UMDE), Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Alberta
authors.initials: A
authors.lastname: Belinchón
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto Carlos III, Madrid, Spain.|Department of Pediatrics, Medical Genetics Section, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Vanesa
authors.initials: V
authors.lastname: López-González
authors.affiliation: Institute of Medical & Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.|Multidisciplinary Skeletal Dysplasia Unit (UMDE), Hospital Universitario La Paz, Madrid, Spain.|Department of Pediatric Endocrinology, Hospital Universitario Infanta Leonor, Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Sentchordi-Montané
authors.affiliation: Institute of Medical & Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto Carlos III, Madrid, Spain.
authors.forename: Ángela
authors.initials: Á
authors.lastname: del Pozo
authors.affiliation: Institute of Medical & Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto Carlos III, Madrid, Spain.|Multidisciplinary Skeletal Dysplasia Unit (UMDE), Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Santos-Simarro
authors.affiliation: Institute of Medical & Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto Carlos III, Madrid, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Campos-Barros
authors.affiliation: Institute of Medical & Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto Carlos III, Madrid, Spain.|Multidisciplinary Skeletal Dysplasia Unit (UMDE), Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto Carlos III, Madrid, Spain.|Department of Pediatrics, Medical Genetics Section, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, Spain.|Cátedra de Genética Médica, UCAM-Universidad Católica San Antonio de Murcia, Spain.
authors.forename: Encarna
authors.initials: E
authors.lastname: Guillén-Navarro
authors.affiliation: Multidisciplinary Skeletal Dysplasia Unit (UMDE), Hospital Universitario La Paz, Madrid, Spain.|Department of Pediatric Endocrinology, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: González-Casado
authors.affiliation: Institute of Medical & Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto Carlos III, Madrid, Spain.|Multidisciplinary Skeletal Dysplasia Unit (UMDE), Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Sixto
authors.initials: S
authors.lastname: García-Miñaur
authors.affiliation: Institute of Medical & Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto Carlos III, Madrid, Spain.|Multidisciplinary Skeletal Dysplasia Unit (UMDE), Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Heath
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D018797:Cell Cycle Proteins; D019465:Craniofacial Abnormalities / Q000235:genetics*; D003598:Cytoskeletal Proteins; D004392:Dwarfism / Q000235:genetics*; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics*; D007223:Infant; D008297:Male; D009133:Muscular Atrophy / Q000235:genetics*; D009260:Nail Diseases / Q000151:congenital / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D013909:Thorax / Q000002:abnormalities
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C575745:POC1A protein, human; D011506:Proteins
keywords: POC1A; SOFT syndrome; centriole; primordial dwarfism; skeletal dysplasia