title: Clinical and molecular description of a 17q21.33 microduplication in a girl with severe kyphoscoliosis and developmental delay.
abstract: High proportion of disease-associated copy number variant maps to chromosome 17. Genomic studies have provided an insight into its complex genomic structure such as relative abundance of segmental duplication and intercepted repetitive elements. 17q21.31, 17q11.2 and 17q12 loci are well known on this chromosome and are associated with microdeletion and microduplication syndrome. No syndrome associated with 17q21.33 locus have been described. We report clinical, cytogenetic and molecular investigations of a 13 years-old girl admitted for evaluation of microcephaly, scoliosis, skeletal defects and learning difficulties. We carried out detailed analysis of the clinical phenotype of this patient and investigated the genetic basis using Agilent 180K Array Comparative Genomic Hybridization. We identified a ∼0.9 Mb de novo microduplication on chromosome 17q21.33. Four genes, COL1A1, SGCA, PPP1R9B and CHAD located within the duplicated region are possible candidates for clinical features present in our patients. Gene expression studies by real-time RT-PCR assay only showed an overexpression of SGCA (P < 0.01), a component of the dystrophin glycoprotein complex. Defect of SGCA was previously shown to lead to severe childhood autosomal recessive muscular dystrophy (LGMD2D) which result in progressive muscle weakness and can also be associated with hyperlordosis or scoliosis. Further cases with similar duplications are expected to be diagnosed. This will contribute to the delineation of this potential new microduplication syndrome and to improve genetic counseling.
authors.affiliation: Univ Clermont 1, UFR Médecine, Cytologie Histologie Embryologie Cytogénétique, Clermont-Ferrand, F-63001, France; CHU Estaing, Cytogénétique Médicale, Clermont-Ferrand, F-63003, France; ERTICa, Univ Clermont 1, UFR Médecine, Clermont-Ferrand, F-63001, France. Electronic address: skemeny@chu-clermontferrand.fr.
authors.forename: Stéphan
authors.initials: S
authors.lastname: Kemeny
authors.affiliation: Univ Clermont 1, UFR Médecine, Cytologie Histologie Embryologie Cytogénétique, Clermont-Ferrand, F-63001, France; CHU Estaing, Cytogénétique Médicale, Clermont-Ferrand, F-63003, France; ERTICa, Univ Clermont 1, UFR Médecine, Clermont-Ferrand, F-63001, France. Electronic address: cpebrel@chu-clermontferrand.fr.
authors.forename: Céline
authors.initials: C
authors.lastname: Pebrel-Richard
authors.affiliation: Univ Clermont 1, UFR Médecine, Cytologie Histologie Embryologie Cytogénétique, Clermont-Ferrand, F-63001, France; CHU Estaing, Cytogénétique Médicale, Clermont-Ferrand, F-63003, France; ERTICa, Univ Clermont 1, UFR Médecine, Clermont-Ferrand, F-63001, France. Electronic address: e_pierre@chu-clermontferrand.fr.
authors.forename: Eléonore
authors.initials: E
authors.lastname: Eymard-Pierre
authors.affiliation: Univ Clermont 1, UFR Médecine, Cytologie Histologie Embryologie Cytogénétique, Clermont-Ferrand, F-63001, France; CHU Estaing, Cytogénétique Médicale, Clermont-Ferrand, F-63003, France; ERTICa, Univ Clermont 1, UFR Médecine, Clermont-Ferrand, F-63001, France. Electronic address: mgay-bellile@chu-clermontferrand.fr.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Gay-Bellile
authors.affiliation: Univ Clermont 1, UFR Médecine, Cytologie Histologie Embryologie Cytogénétique, Clermont-Ferrand, F-63001, France; CHU Estaing, Cytogénétique Médicale, Clermont-Ferrand, F-63003, France; ERTICa, Univ Clermont 1, UFR Médecine, Clermont-Ferrand, F-63001, France. Electronic address: lgouas@chu-clermontferrand.fr.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Gouas
authors.affiliation: Univ Clermont 1, UFR Médecine, Cytologie Histologie Embryologie Cytogénétique, Clermont-Ferrand, F-63001, France; CHU Estaing, Cytogénétique Médicale, Clermont-Ferrand, F-63003, France; ERTICa, Univ Clermont 1, UFR Médecine, Clermont-Ferrand, F-63001, France. Electronic address: cgoumy@chu-clermontferrand.fr.
authors.forename: Carole
authors.initials: C
authors.lastname: Goumy
authors.affiliation: Univ Clermont 1, UFR Médecine, Cytologie Histologie Embryologie Cytogénétique, Clermont-Ferrand, F-63001, France; CHU Estaing, Cytogénétique Médicale, Clermont-Ferrand, F-63003, France; ERTICa, Univ Clermont 1, UFR Médecine, Clermont-Ferrand, F-63001, France. Electronic address: atchirkov@chu-clermontferrand.fr.
authors.forename: Andreï
authors.initials: A
authors.lastname: Tchirkov
authors.affiliation: CHU Estaing, Génétique Médicale, Clermont-Ferrand, F-63000, France. Electronic address: cfrancannet@chu-clermontferrand.fr.
authors.forename: Christine
authors.initials: C
authors.lastname: Francannet
authors.affiliation: Univ Clermont 1, UFR Médecine, Cytologie Histologie Embryologie Cytogénétique, Clermont-Ferrand, F-63001, France; CHU Estaing, Cytogénétique Médicale, Clermont-Ferrand, F-63003, France; ERTICa, Univ Clermont 1, UFR Médecine, Clermont-Ferrand, F-63001, France. Electronic address: pvago@chu-clermontferrand.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vago
mesh_terms: D000293:Adolescent; D002886:Chromosomes, Human, Pair 17; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D020440:Gene Duplication; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008831:Microcephaly / Q000235:genetics; D009139:Musculoskeletal Abnormalities / Q000235:genetics; D054645:Protein Phosphatase 1 / Q000235:genetics; D049031:Sarcoglycans / Q000235:genetics; D012600:Scoliosis / Q000235:genetics
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D016326:Extracellular Matrix Proteins; C526571:SGCA protein, human; D049031:Sarcoglycans; C088980:chondroadherin; D054645:Protein Phosphatase 1
keywords: 17q21.33 microduplication; Developmental delay; SGCA gene; Scoliosis