Molecular characterization of a de novo 6q24.2q25.3 duplication interrupting UTRN in a patient with arthrogryposis.
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.
Tabet
Anne-Claude
AC
AP-HP, Cytogenetics Unit, Department of Genetics, Robert Debré Hospital, Paris, France. anne-claude.tabet@rdb.aphp.fr
Aboura
Azzedine
A
Gérard
Marion
M
Pilorge
Marion
M
Dupont
Céline
C
Gadisseux
Jean-François
JF
Hervy
Nadège
N
Pipiras
Eva
E
Delahaye
Andrée
A
Kanafani
Samia
S
Verloes
Alain
A
Benzacken
Brigitte
B
Betancur
Catalina
C
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*
C483599:UTRN protein, human; D049411:Utrophin