title: Molecular characterization of a de novo 6q24.2q25.3 duplication interrupting UTRN in a patient with arthrogryposis.
abstract: Chromosome 6q duplications have been documented repeatedly, allowing the delineation of a "6q duplication syndrome," characterized by hypertelorism, downslanting palpebral fissures, tented upper lip, short neck, severe mental and growth retardation, and joint contractures. Most reported cases result from malsegregation of a reciprocal translocation leading to a terminal 6q duplication and partial monosomy of another chromosome. Only 11 cases of de novo pure duplication have been reported so far. The breakpoints do not appear to be recurrent, but in most cases they have not been characterized molecularly, precluding genotype-phenotype correlation. We report on an 8-year-old girl with a phenotype consistent with mild 6q duplication syndrome, including characteristic physical findings, mild mental retardation, and joint contractures. She carries a 13 Mb de novo 6q24.2q25.3 duplication, diagnosed by high-resolution karyotype and confirmed by array-CGH. Molecular characterization of the duplicated segment with quantitative PCR showed that the proximal breakpoint is localized within the UTRN gene, encoding utrophin, the autosomal homologue of dystrophin. We discuss the possible implication of UTRN in arthrogryposis associated with duplications spanning the 6q23q26 region.
authors.affiliation: AP-HP, Cytogenetics Unit, Department of Genetics, Robert Debré Hospital, Paris, France. anne-claude.tabet@rdb.aphp.fr
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Tabet
authors.forename: Azzedine
authors.initials: A
authors.lastname: Aboura
authors.forename: Marion
authors.initials: M
authors.lastname: Gérard
authors.forename: Marion
authors.initials: M
authors.lastname: Pilorge
authors.forename: Céline
authors.initials: C
authors.lastname: Dupont
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gadisseux
authors.forename: Nadège
authors.initials: N
authors.lastname: Hervy
authors.forename: Eva
authors.initials: E
authors.lastname: Pipiras
authors.forename: Andrée
authors.initials: A
authors.lastname: Delahaye
authors.forename: Samia
authors.initials: S
authors.lastname: Kanafani
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.forename: Brigitte
authors.initials: B
authors.lastname: Benzacken
authors.forename: Catalina
authors.initials: C
authors.lastname: Betancur
mesh_terms: D001176:Arthrogryposis / Q000150:complications / Q000235:genetics*; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D020440:Gene Duplication; D006228:Hand Deformities, Congenital / Q000150:complications / Q000000981:diagnostic imaging; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011859:Radiography; D049411:Utrophin / Q000235:genetics*
chemical_list: C483599:UTRN protein, human; D049411:Utrophin